InnateDB Innate Immunity Genes

Aside from annotating innate immunity interactions and pathways, the InnateDB curation team has also established a project to annotate genes that have a role in the innate immune response. This has been initiated in response to the fact that Gene Ontology annotation of the innate immune response is quite limited in the numbers of genes which have been identified and in response to the fact that many users have been eager to have a defined list of innate immune genes. For innate immune gene annotation, curators employ a new tool in the InnateDB curation system to associate relevant genes with publications which provide evidence for that gene having a role in innate immunity. Along with the link to the relevant publication(s), the curators provide a one-line summary of the role similar to Entrez GeneRIFs. Such genes are also automatically associated with the Gene Ontology term "innate immune response" in InnateDB, which provides a more comprehensive list of these genes for use in the InnateDB Gene Ontology over-representation analysis tool. To date, 1688 genes have been annotated to some extent (as this is an on-going process). It should be noted that it is not the intention of InnateDB to comprehensively annotate all the roles of a given gene, but rather to provide a brief indication if a gene has a role in innate immunity. You can download all InnateDB curated genes with their annotations as Excel sheet.

This list provides details of the 2303 genes which have been annotated by either InnateDB or Gene Ontology as having a role in the innate immune response and is updated weekly.

Review the latest annotations: Download View all
Gene name Annotation Added
TLR2 (Homo sapiens) PubMed 20505832: TLR2 plays a critical role in the ability of innate immunity to determine M. pulmonis numbers in the lung, and early after respiratory infection TLR2 recognition of M. pulmonis triggers initial cytokine responses of host cells.
PubMed 20927103: TLR2 functions as a sensor of oxidation-associated molecular patterns, providing a key link connecting inflammation, oxidative stress, innate immunity and angiogenesis.
PubMed 21439957: TLR1 :: TLR2 dimeric pairs recognize malarial glycosylphosphatidylinositols (GPI) to initiates intracellular signalling and the production of pro-inflammatory cytokines.
PubMed 21454596: TLR2 recognizes Thermus aquaticus extracellular polysacchride, YT-1, and induces the production of cytokines TNF and IL6 in peritoneal macrophages. (Demonstrated in murine model)
PubMed 21482737: TLR2::TLR6 synergistically interacts with TLR9 in lung epithelium to induce rapid pathogen killing, and can be used as a therapeutic target to treat otherwise lethal pneumonia.
PubMed 21512004: TLR2 is activated by gut commensal microbe, Bacteroides fragilis, to establish host-microbial symbiosis by promoting immunological tolerance. (Demonstrated in murine model)
PubMed 21566133: TLR2 and TNFSF11 signalling pathways are modulated by Porphromonas gingivalis to alter the differentiation states of osteoclasts resulting in bacteria-mediated bone loss. (Demonstrated in murine model)
PubMed 21602496: TLR2 is expressed by Muller cells, principal glia of retina, and is responsible for generating robust bactericidal activity against Staphylococcus aureus and contributing to retinal innate defence.
PubMed 21698237: TLR2 is required for rapid inflammasome activation in response to infection by cytosolic bacterial pathogens such as Francisella novicida. (Demonstrated in murine model)
PubMed 21862586: TLR2-driven integration of inducible nitric oxide synthase (iNOS), Wnt-beta-Catenin and NOTCH1 signalling contributes to its capacity to regulate a battery of genes associated with T regulatory cell lineage commitment and towards modulation of defined set of effector functions in macrophages. (Demonstrated in murine model)
PubMed 21873606: TLR2 directly recognizes glycogen, resulting in the activation of immunocytes such as macrophages to enhance the production of nitric oxide and inflammatory cytokines.
PubMed 22096480: TLR2 and TLR4 are crucial for in vivo recognition of Chlamydia pneumoniae. Tlr2/4 double-deficient mice were unable to control pneumonia caused by C. pneumoniae. (Demonstrated in mice)
PubMed 22102818: TLR2 signalling promotes protective vaccine-enhancing Th17 cell responses when cells are stimulated with early secreted antigenic target protein 6 (ESAT-6) expressed by the virulent Mycobacterium tuberculosis strain H37Rv but not by tuberculosis vaccine Bacillus Calmette-Guérin (BCG). (Demonstrated in mice)
PubMed 22174456: TLR2 recognizes Mycobacterium tuberculosis H37Rv cell surface lipoprotein MPT83, which induces the production of TNF, IL6, and IL12B cytokines by macrophages and upregulates macrophage function. (Demonstrated in mouse)
PubMed 22216191: Mycobacterium abscessus glycopeptidolipid (GPL) prevents TLR2-mediate induction of IL8 and DEFB4A in respiratory epithelial cells.
PubMed 25353353: Interaction of filamentous hemagglutinin (FHA) with TLR2 induces an innate immune response against Bordetella pertussis and the TLR2-binding domain of FHA may contribute to immunoprotection against pertussis infection.
PubMed 25456159: Cutaneous bacteria can negatively regulate skin-driven immune responses by inducing Gr1(+)CD11b(+) myeloid-derived suppressor cells via TLR2-6 activation.
PubMed 25531754: Soluble TLR2 (sTLR2) generated by metalloproteinase activation inhibits TLR2-induced cytokine production in THP-1 cell line.
PubMed 25977263: TLR10 is a functional receptor involved in the innate immune response to H. pylori infection and the TLR2/TLR10 heterodimer functions in H. pylori lipopolysaccharide recognition.
PubMed 25955717: Human Cytomegalovirus (HCMV) miR-UL112-3p efficiently targets TLR2 during HCMV infection, resulting in the inhibition of TLR2-mediated NFκB signalling.
PubMed 26610398: H. pylori infection induces the expression and activation of components of NLRP3 inflammasomes in neutrophils and this activation is independent of a functional type IV secretion system, TLR2 and TLR4.
PubMed 26283364: Staphylococcal superantigen-like protein 3 (SSL3) interferes with TLR2 activation at two stages. First by binding to TLR2 and blocking ligand binding and second by interacting with an already formed TLR2-lipopeptide complex, thus preventing TLR heterodimerization and downstream signalling.
PubMed 26310831: PELI3 is involved in endotoxin tolerance and functions as a negative regulator of TLR2/4 signalling.
2017-05-25
PELI3 (Homo sapiens) PubMed 17997719: PELI3 and other pellino isoforms are the E3 ubiquitin ligases that mediate the IL-1-stimulated formation of K63-pUb-IRAK1 in cells, which may contribute to the activation of IKBKB and NF-kappaB, as well as other signalling pathways dependent on IRAK1 and IRAK4.
PubMed 25483963: Autophagy causes PELI3 degradation during Tlr4-signalling, subsequently inhibiting Il1b expression and impairing the hyperinflammatory phase during sepsis.
PubMed 26310831: PELI3 is involved in endotoxin tolerance and functions as a negative regulator of TLR2/4 signalling.
2017-05-25
IL1B (Homo sapiens) PubMed 20195505: IL1B is an important proinflammatory cytokine that activates monocytes, macropages, and neutrophils. IL1B processing during infection is a complex process in which the inflammasomes are only one of several activation mechanisms.
PubMed 20401526: Mature IL1B production requires, in addition to the synthesis of pro-IL1B, cleavage of the precursor protein by the inflammatory CASP1 (Caspase-1) which is controlled within the NLRP3 inflammasome.
PubMed 20620944: IL1B-producing conventional dendritic cells preserves and expands IL-22(+)AHR(+) immature human natural killer cells in the secondary lymphoid tissue.
PubMed 21170027: IL1B acts as a growth factor for neutrophil progenitors and as a survival factor for mature neutrophils. In the absence of IKBKB, the IL1B production is enhanced and provides a compensatory mechanism for maintaining antibacterial defense when NFKB is inhibited. (Demonstrated in murine model)
PubMed 21228274: IL1B secretion in macrophages is regulated by autophagy by two mechanisms; sequestering of pro-IL1B in autophagosome during TLR stimulation, and processing,secretion of IL1B in a NLRP3- and TRIF-dependent manner.
PubMed 21602824: IL1B secretion is induced only during viable E. coli infection (as oppose to heat-killed E. coli or LPS); Viable bacteria specifically elicit cleavage of pro-IL1B. (Demonstrated in murine model)
PubMed 21270399: IL1B derived from alveolar macrophages is the critical mediator which induces chemokine production in non-hematopoietic cells in the lung, resulting in swift and robust recruitment of infection-controlling neutrophils into the airways. (Demonstrated in murine model)
PubMed 21628463: IL1B secretion is tightly regulated by the redox status in myeloid cells. TLR engagement in monocytes induces ROS generation followed by a sustained antioxidant response and efficient IL1B secretion. In macrophages, the antioxidant systems are in an upregulated state, and therefore buffers the TLR induction of the redox response, which results in low IL1B processing and secretion.
PubMed 22158745: IL1B is an important component of the cellular network involving macrophages and epithelial cells, which facilitates IL8 chemokine expression and aids neutrophil recruitment during pneumococcal pneumonia.
PubMed 22426547: IL1B is an inflammatory cytokine that binds to its primary receptor, IL1R1, that then recruits the accessory protein IL1RAP to form a signalling-competent heterotrimeric complex.
PubMed 24277153: TLR8 plays a pathogenic role in disease whereby its expression is increased in patients with systemic arthritis and is correlated with the elevation of IL1B levels and disease status.
PubMed 24323452: Protein-bound polysaccharide-K can activate the NLRP3 inflammasome and induce IL1B in a TLR2- and NLRP3-dependent manner.
PubMed 25463072: Interleukin-1 (IL1A/IL1B) plays a key role in the interaction between local vessel wall cells and invading monocytes to multiply cholesterol-triggered inflammation in the vessel wall.
PubMed 25474109: IFNG interferes with the IL-1/NFKBIZ axis in β-glucan-activated dendritic cells and promotes T cell-mediated immune responses with increased release of IFNG and IL22, and diminished production of IL17A.
PubMed 25964352: CASP4 is a critical regulator of noncanonical inflammasome activation that initiates defence against bacterial pathogens in primary macrophages by mediating cell death and IL1A release
PubMed 25637949: DEFB103A and RNASE7 are induced in human umbilical endothelial cells (HUVECs) by classical inflammatory cytokines such as: IFNG, IL1B and TNF.
PubMed 26032420: Antibody-dependent enhancement (ADE) of Dengue virus serotype 2 (DENV-2) elevates mature IL1B secretion via SYK signalling pathway in primary monocytes.
PubMed 26187413: Differentiation of Type 3 innate lymphoid cells (ILC3) to IL7R(+) ILC1 is reversible whereas IL7R(+) ILC1 can differentiate to ILC3 in the presence of IL2, IL23A, and IL1B dependent on the transcription factor RORC, and this process is enhanced in the presence of retinoic acid.
PubMed 26324708: 20-kDa IL1B generated from CASP1 cleaved pro-IL1B limits the available pro-IL1B for generation of CASP1 cleaved 17-kDa IL1B, thus reducing inflammation.
2017-05-25
CASP1 (Homo sapiens) PubMed 15039421: CASP1 activates NF-kappaB independent of its enzymatic activity and contributes to inflammation by proteolysis of pro-IL1B (IL-1 beta) and RIPK2 activation of NF-kappaB and MAPK1.
PubMed 19124602: CASP1 is part of the inflammasome complex, along with pathogen-specific nucleotide oligomerization and binding domain (NOD)-like receptors (NLRs) and in some cases the scaffolding protein ASC. Formation of the membrane-associated inflammasome complex in murine macrophages, results in cleavage of cytosolic CASP1 substrates and cell death.
PubMed 20823203: CASP1 activity is required for discrimination between translocon-positive and -negative bacteria in bone-marrow derived cells and interleukin-1 receptor signalling. Activation of CASP1 by bacteria expressing Type 3 secretion systems allows for rapid recognition of bacteria expressing conserved functions associated with virulence.
PubMed 21057511: CASP1 clears intracellular bacteria in vivo independently of IL1B (IL-1-beta) and IL18 and establishes pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system. CASP1-induced pyroptotic cell death releases bacteria from macrophages and exposes the bacteria to uptake and killing by reactive oxygen species in neutrophils.
PubMed 21439959: CASP1 is a component of the inflammasome and is required for inflammation in acute pancreatitis. (Demonstrated in murine model)
PubMed 21602824: CASP1-dependent inflammatory cell death, or pyroptosis, is only induced by viable, but not heat-killed, E. coli. (Demonstrated in murine model)
PubMed 22833538: Naturally occurring variants of CASP1 differ considerably in structure and the ability to activate IL1B.
PubMed 24481253: The precursor and mature forms of IL37 are secreted from activated cells upon inflammasome activation and CASP1 processing of IL37 is important for its anti-inflammatory activity.
PubMed 26324708: 20-kDa IL1B generated from CASP1 cleaved pro-IL1B limits the available pro-IL1B for generation of CASP1 cleaved 17-kDa IL1B, thus reducing inflammation.
2017-05-25
TLR4 (Homo sapiens) PubMed 18326860: TLR4 is activated by LPS and this recognition activates the Src family kinases, Src, Fyn and Yes, which in turn contribute to tyrosine phosphorylation of Zonula adherens proteins to open the endothelial paracellular pathway.
PubMed 15852007: TLR4 binding to microbial ligands can be inhibited by CD180 and its helper molecule, LY86, via direct interactions with the TLR4 signalling complex.
PubMed 10196138: TLR4 is involved in lipopolysaccharide (LPS) signaling and serves as a cell-surface co-receptor for CD14, leading to LPS-mediated NF-kappaB activation and subsequent cellular events.
PubMed 20037584: TLR4-TLR6-Cd36 activation is a common molecular mechanism by which atherogenic lipids and amyloid-beta stimulate sterile inflammation.
PubMed 20133493: TLR4 dimerize and enable rapid signal transduction against LPS stimulation on membrane-associated CD14-expressing cells.
PubMed 20360853: TLR4 and TLR9 have both non-redundant and cooperative roles in lung innate responses during Gram-negative bacterial pneumonia and are both critical for IL-17 driven antibacterial host response.
PubMed 20826541: TLR4 mediates LPS-induced muscle catabolism via coordinate activation of the ubiquitin-proteasome and the autophagy-lysosomal pathways. TLR4 activation by LPS induces C2C12 myotube atrophy via up-regulating autophagosome formation and the expression of ubiquitin ligase atrogin-1/MAFbx and MuRF1.
PubMed 21442393: TLR4 transfection of eukaryotic host cells using bacterial vectors, or bactofection, was shown to reduce E. coli colonization in the kidney and the bladder in an animal model of urinary tract infection. (Demonstrated in murine model)
PubMed 21464300: TLR4 is involved in the transmission of ER stress from tumour cells to macrophages, promoting a pro-inflammatory program in the tumour microenvironment, thus facilitating tumour progression. (Demonstrated in murine model)
PubMed 21518783: TLR4 deficient murine macrophages results in the complete abrogation of TNF-alpha production during Leishmania panamensis infection. The endosomal TLR4 plays a crucial role in the activation of host macrophages and controlling the early stages of parasitic infection. (Demonstrated in murine model)
PubMed 21615666: Epithelial TLR4 activation facilitates the transcytosis of non-cytolytic uropathogenic E. coli across intact collecting duct cell layers to invade the renal interstitium in experimental urinary tract infections.
PubMed 21712422: TLR4:LY96 functions as intracellular LPS sensor and triggers a unique set of LPS responses upon recognition of phagocytosed bacteria in macrophages. (Demonstrated in murine model)
PubMed 21730052: TLR4 on dendritic cell surfaces binds to HSPA14 and induces a robust Th1 response via the MAPK and NFkB signalling pathways. (Demonstrated in mouse)
PubMed 21738466: TLR4 recognizes Clostridium difficile surface layer proteins and induces the maturation of dendritic cells to activate the innate and adaptive immune response. (Demonstrated in mouse)
PubMed 21775438: TLR4 and HSPD1 mediate myocardial ischemia-activated innate immune signalling, which plays an important role in mediating apoptosis and inflammation during ischemia/reperfusion (I/R). (Demonstrated in murine model)
PubMed 22096480: TLR4 and TLR2 are crucial for in vivo recognition of Chlamydia pneumoniae. Tlr4/2 double-deficient mice were unable to control pneumonia caused by C. pneumoniae. (Demonstrated in mice)
PubMed 22354030: TLR4 translocates to membrane lipid rafts in a ceramide-dependent manner in Helicobacter pylori infected gastric epithelial cells.
PubMed 22396536: TLR4 is involved in cell-cell contact signalling between activated apoptotic lymphocytes and dendritic cells (DC) during the maturation of DCs.
PubMed 22433865: Synthetic triacylated lipid A-molecules have the potent ability to selectively antagonize TLR4 and inhibit anti-bacterial immunity.
PubMed 22593572: The poxviral protein A46 directly inhibits TLR4 signalling by disrupting receptor complex formation.
PubMed 22962435: A human TLR4 polymorphism (D299G/T399I) impairs TLR4::LY96 dimerization and results in a dampened host response to bacterial lipids.
PubMed 22951730: TLR4 is an important regulator of wound inflammation and is essential for early skin wound healing. (Demonstrated in mice)
PubMed 24265315: TIR domain-contaning protein from Brucella melitensis, TcpB, disrupts the receptor-adaptor interaction between TLR4 and TIRAP.
PubMed 25371197: ECSIT binds to MAP3K7 and TRAF6 to form a complex that plays a pivotal role in activating TLR4-mediated NF-kB signalling.
PubMed 25505274: The TLR4/S100A8 axis is important in the activation of monocytes.
PubMed 26082489: Endotoxin tolerance re-programs TLR4 signalling via suppression of PELI1, a positive regulator of MyD88- and TIR domain-containing adapter inducing IFN-β (TRIF)-dependent signalling that promotes K63-linked polyubiquitination of IRAK1, TBK1, and TAK1.
PubMed 26610398: H. pylori infection induces the expression and activation of components of NLRP3 inflammasomes in neutrophils and this activation is independent of a functional type IV secretion system, TLR2 and TLR4.
PubMed 26310831: PELI3 is involved in endotoxin tolerance and functions as a negative regulator of TLR2/4 signalling.
2017-05-25
Peli3 (Mus musculus) PubMed 26310831: Peli3 is involved in endotoxin tolerance and functions as a negative regulator of Tlr2/4 signalling.
2017-05-25
Ube2i (Mus musculus) PubMed 26348439: Baiap2l1 recruits Ube2i to sumoylate Pcbp2, which causes its cytoplasmic translocation during viral infection and the sumoylated Pcbp2 associates with Mavs to initiate its degradation, leading to downregulation of antiviral responses.
2017-05-25
Tlr2 (Mus musculus) PubMed 18768838: Tlr2 expression in astrocytes is induced by TNF alpha and NF Kappa B-dependent pathways.
PubMed 18621910: Tlr2 recognition of Staphylococcal peptidoglycan leads to induction of beta-defensin-2.
PubMed 19019963: Tlr2 is involved in Respiratory syncytial virus (RSV) recognition and subsequent innate immune activation by promoting neutrophil migration and dendritic cell activation within the lung.
PubMed 19865078: Tlr4, Tlr2, or Tlr3 cooperate with proteinase-activated receptors (PARs) for activation of nuclear factor-kappaB-dependent signaling in mucosal epithelial cell lines.
PubMed 9751057: Tlr2 is a signaling receptor that is activated by lipopolysaccharide (LPS) in a response that depends on LPS-binding protein and is enhanced by CD14.
PubMed 10364168: Tlr2 is a signal transducer for soluble Peptidoglycan and lipoteichoic acid (LTA) in addition to LPS.
PubMed 10384090: Tlr2 recognizes Gram-positive bacterial cell wall components, leading to the activation of the innate immune system.
PubMed 10426996: Tlr2 is a molecular link between microbial products, apoptosis, and host defense mechanisms.
PubMed 20167866: TLR2/MyD88/PI3K/Rac1/Akt pathway mediates the activation of LTA-induced mitogen-activated protein kinases (MAPKs), which in turn initiates the activation of NF-kappaB, and ultimately induces cPLA2/COX-2-dependent PGE2 and IL-6 generation.
PubMed 20385881: Tlr2 and Tlr4 activate murine macrophages and this is negatively regulated by a Lyn/PI3K module and promoted by SHIP1.
PubMed 20407745: Tlr2 is a molecular link between increased dietary lipid intake and the regulation of glucose homeostasis, via regulation of energy substrate utilization and tissue inflammation.
PubMed 20422028: Tlr2 activation induces type I interferon responses from endolysosomal compartments where it is translocated to upon ligand engagement.
PubMed 20368346: Tlr2 and Myd88-dependent phosphatidylinositol 3-kinase and Rac1 activation facilitates the phagocytosis of Listeria monocytogenes by murine macrophages.
PubMed 21439957: Tlr1 :: Tlr2 dimeric pairs recognize malarial glycosylphosphatidylinositols (GPI) to initiates intracellular signalling and the production of pro-inflammatory cytokines.
PubMed 21454596: Tlr2 recognizes Thermus aquaticus extracellular polysacchride, YT-1, and induces the production of cytokines TNF and IL6 in peritoneal macrophages.
PubMed 21482737: Tlr2::Tlr6 synergistically interacts with Tlr9 in lung epithelium to induce rapid pathogen killing, and can be used as a therapeutic target to treat otherwise lethal pneumonia.
PubMed 21512004: Tlr2 is activated by gut commensal microbe, Bacteroides fragilis, to establish host-microbial symbiosis by promoting immunological tolerance.
PubMed 21566133: Tlr2 and Tnfsf11 signalling pathways are modulated by Porphromonas gingivalis to alter the differentiation states of osteoclasts resulting in bacteria-mediated bone loss.
PubMed 21602496: Tlr2 is expressed by Muller cells, principal glia of retina, and is responsible for generating robust bactericidal activity against Staphylococcus aureusand contributing to retinal innate defence.
PubMed 21698237: Tlr2 is required for rapid inflammasome activation in response to infection by cytosolic bacterial pathogens such as Francisella novicida.
PubMed 21862586: Tlr2-driven integration of inducible nitric oxide synthase (iNOS), Wnt-beta-Catenin and Notch1 signalling contributes to its capacity to regulate a battery of genes associated with T regulatory cell lineage commitment and towards modulation of defined set of effector functions in macrophages.
PubMed 21873606: Tlr2 directly recognizes glycogen, resulting in the activation of immunocytes such as macrophages to enhance the production of nitric oxide and inflammatory cytokines.
PubMed 22096480: Tlr2 and Tlr4 are crucial for in vivo recognition of Chlamydia pneumoniae. Tlr2/4 double-deficient mice were unable to control pneumonia caused by C. pneumoniae.
PubMed 22102818: Tlr2 signalling promotes protective vaccine-enhancing Th17 cell responses when cells are stimulated with early secreted antigenic target protein 6 (ESAT-6) expressed by the virulent Mycobacterium tuberculosis strain H37Rv but not by tuberculosis vaccine Bacillus Calmette-Guérin (BCG).
PubMed 22174456: Tlr2 recognizes Mycobacterium tuberculosis H37Rv cell surface lipoprotein MPT83, which induces the production of Tnf, Il6, and Il12b cytokines by macrophages and upregulates macrophage function.
PubMed 22216191: Mycobacterium abscessus glycopeptidolipid (GPL) prevents Tlr2-mediate induction of Il8 and Defb4a in respiratory epithelial cells. (Demonstrated in human)
PubMed 23994200: Tlr2 is expressed in the enteric nervous system (ENS) and intestinal smooth muscle layers. Its absence induces architectural and neurochemical coding changes in the ENS, leading to gut dysmotility and to higher inflammatory bowel diseases susceptibility
PubMed 25423082: Salmonella enterica serovar Typhimurium ?msbB that possesses a modified lipid A triggers exacerbated colitis in the absence of Nod1 and/or Nod2, which is likely due to increased Tlr2 stimulation.
PubMed 25505250: Adaptor proteins Ticam1 and Ticam2 have a novel function in Tlr2-mediated signal transduction.
PubMed 25826367: Retinoic acid treatment enhances Tlr2-dependent Il10 production from T cells and this, in turn, potentiates T regulatory cell generation without the need for activation of antigen presenting cells.
PubMed 25586105: Proline-proline-glutamic acid 57 (PPE57), located on the mycobacterial cell surface, induces a T helper 1 immune response via Tlr2-mediated macrophage functions.
PubMed 26078314: Tlr2 is essential for the immune responses to cholera vaccination.
PubMed 26283364: Staphylococcal superantigen-like protein 3 (SSL3) interferes with Tlr2 activation at two stages. First by binding to Tlr2 and blocking ligand binding and second by interacting with an already formed Tlr2-lipopeptide complex, thus preventing TLR heterodimerization and downstream signalling.
PubMed 26310831: Peli3 is involved in endotoxin tolerance and functions as a negative regulator of Tlr2/4 signalling.
2017-05-25
Tlr4 (Mus musculus) PubMed 19923461: Signaling crosstalk during sequential Tlr4 and Tlr9 activation amplifies the inflammatory response of mouse macrophages.
PubMed 20385881: Tlr4 and Tlr2 activate murine macrophages and this activation is negatively regulated by a Lyn/PI3K module and promoted by SHIP1.
PubMed 21442393: Tlr4 transfection of eukaryotic host cells using bacterial vectors, or bactofection, was shown to reduce E. coli colonization in the kidney and the bladder in an animal model of urinary tract infection.
PubMed 21464300: Tlr4 is involved in the transmission of ER stress from tumour cells to macrophages, promoting a pro-inflammatory program in the tumour microenvironment, thus facilitating tumour progression.
PubMed 21518783: Tlr4 deficient murine macrophages results in the complete abrogation of TNF-alpha production during Leishmania panamensis infection. The endosomal Tlr4 plays a cruical role in the activation of host macrophages and controlling the early stages of parasitic infection.
PubMed 21615666: Epithelial Tlr4 activation facilitates the transcytosis of non-cytolytic uropathogenic E. coli across intact collecting duct cell layers to invade the renal interstitium in experimental urinary tract infections.
PubMed 21712422: Tlr4:Ly96 functions as intracellular LPS sensor and triggers a unique set of LPS responses upon recognition of phagocytosed bacteria in macrophages.
PubMed 21730052: Tlr4 on dendritic cell surfaces binds to Hspa14 and induces a robust Th1 response via the MAPK and NFkB signalling pathways.
PubMed 21738466: Tlr4 recognizes Clostridium difficile surface layer proteins and induces the maturation of dendritic cells to activate the innate and adaptive immune response.
PubMed 21775438: Tlr4 and Hspd1 mediate myocardial ischemia-activated innate immune signalling, which plays an important role in mediating apoptosis and inflammation during ischemia/reperfusion (I/R).
PubMed 22096480: Tlr4 and Tlr2 are crucial for in vivo recognition of Chlamydia pneumoniae. Tlr4/2 double-deficient mice were unable to control pneumonia caused by C. pneumoniae.
PubMed 22354030: Tlr4 translocates to membrane lipid rafts in a ceramide-dependent manner in Helicobacter pylori infected gastric epithelial cells. (Demonstrated in human)
PubMed 22396536: Tlr4 is involved in cell-cell contact signalling between activated apoptotic lymphocytes and dendritic cells (DC) during the maturation of DCs. (Demonstrated in human)
PubMed 22433865: Synthetic triacylated lipid A-molecules have the potent ability to selectively antagonize Tlr4 and inhibit anti-bacterial immunity. (Demonstrated in human)
PubMed 22593572: The poxviral protein A46 directly inhibits Tlr4 signalling by disrupting receptor complex formation. (Demonstrated in human)
PubMed 22962435: A human TLR4 polymorphism (D299G/T399I) impairs TLR4::LY96 dimerization and results in a dampened host response to bacterial lipids. (Demonstrated in human)
PubMed 22951730: Tlr4 is an important regulator of wound inflammation and is essential for early skin wound healing.
PubMed 24101501: Milk oligosaccharide sialyl(α2,3)lactose modulates mucosal immunity by inducing inflammation through TLR4 signaling
PubMed 24423728: Itgam (Cd11b) fine tunes the balance between adaptive and innate immune responses initiated by LPS by modulating the trafficking and signalling functions of Tlr4 in a cell-type-specific manner.
PubMed 24163408: Nod1 and Nod2 synergize with Tlr4 in dendritic cells to increase IL12 production and enhance invariant natural killer T (iNKT) cell activation, and are important regulators of the IFN gamma response by iNKT cells during S. typhimurium and L. monocytogenes infections.
PubMed 25022365: Rab8a interacts with Pik3cg to regulate Akt signalling generated by surface Tlr4.
PubMed 25389373: High-potency Tlr4 agonists can act as clinically useful vaccine adjuvants by selectively activating Ticam1-dependent immunostimulatory signalling events and only weakly activating potentially harmful Myd88-dependent inflammatory responses.
PubMed 25448706: Myd88 and Ticam1 pathways differently regulate Tlr4-induced immune responses in B cells.
PubMed 25483963: Autophagy causes PELI3 degradation during Tlr4-signalling, subsequently inhibiting Il1b expression and impairing the hyperinflammatory phase during sepsis.
PubMed 25549946: Tmem126a upregulates genes involved in antigen presentation; such as Icam1, MHC II, Cd86 and Cd40, via the Tlr4 signal transduction pathway.
PubMed 25548220: Ticam1 but not Myd88 signalling is critical for the Trl4 protective adjuvant effect in neonates; where Ticam1(-/-) but not Myd88(-/-) neonates are highly susceptible to Escherichia coli peritonitis and bacteremia.
PubMed 25736436: Wdfy1 is a crucial adaptor protein in the Tlr3/4 signalling pathway. Wdfy1 interacts with Tlr3 and Tlr4 and mediates the recruitment of Ticam1 to these receptors.
PubMed 25801433: Lipopolysaccharide-mediated myeloid Anpep (CD13) expression governs internalization of Tlr4 and negatively regulates Tlr4 signalling, thereby balancing the innate response by maintaining the inflammatory equilibrium critical to innate immune regulation.
PubMed 26081153: Psen2 deficiency is paralleled by reduced transcription of Tlr4 mRNA and loss of LPS-induced Tlr4 mRNA transcription regulation.
PubMed 26310831: Peli3 is involved in endotoxin tolerance and functions as a negative regulator of Tlr2/4 signalling.
2017-05-25
Baiap2l1 (Mus musculus) PubMed 26348439: Baiap2l1 recruits Ube2i to sumoylate Pcbp2, which causes its cytoplasmic translocation during viral infection and the sumoylated Pcbp2 associates with Mavs to initiate its degradation, leading to downregulation of antiviral responses.
2017-05-25
COLEC12 (Homo sapiens) PubMed 26290605: Soluble COLEC12 can recognize Aspergillus fumigatus leading to activation of the alternative pathway of complement.
2017-05-18
IL6 (Homo sapiens) PubMed 21148800: IL6 trans-signalling via STAT3 is a critical modulator of LPS-driven pro-inflammatory responses through cross-talk regulation of the TLR4/Mal signalling pathway broader mechanism that regulates the severity of the host inflammatory response.
PubMed 22096605: IL6 synthesis is regulated by the opposing effects of prostaglandin (PG)E(2) and PGD(2) in human chondrocytes. IL6 synthesis is increased by PGE2 and decreased by PGD2 through the modulation of TLR4 synthesis.
PubMed 22030478: Activation of either TLR4 or TLR2/6 significantly increased IL6 expression by U937 mononuclear cells. Co-activation of TLR4 and TLR2/6, led to a further augmentation on IL-6 expression.
PubMed 22426116: IL6 is strategically upregulated by virulent Mycobacterium tuberculosis to inhibit the induction of innate immunity.
PubMed 23735697: Hyperglycemia abrogates the ability of IL6 to induce neutrophil extracellular traps.
PubMed 24012417: IFN gamma creates a primed chromatin environment in macrophages to augment TLR-induced IL6 transcription
PubMed 26287468: TET2 selectively mediates active repression of IL6 transcription via NFKBIZ and HDAC2 during inflammation resolution in innate myeloid cells, including dendritic cells and macrophages.
2017-05-18
CLEC4E (Homo sapiens) PubMed 21267996: CLEC4E, a C-type lectin receptor, is a pattern recognition receptor critical for immune responses to fungi. CLEC4E is coupled to SYK kinase and signals via CARD9 to activate NFKB, which in turns induces both innate and adaptive immunity.
PubMed 24733387: Glycerol monomycolate is a unique ligand for CLEC4E (Mincle).
PubMed 26296894: Cholesterol crystals are an endogenous ligand for CLEC4E and their binding activates innate immune responses.
2017-05-18
TET2 (Homo sapiens) PubMed 26287468: TET2 selectively mediates active repression of IL6 transcription via NFKBIZ and HDAC2 during inflammation resolution in innate myeloid cells, including dendritic cells and macrophages.
2017-05-18
TLR2 (Homo sapiens) PubMed 20505832: TLR2 plays a critical role in the ability of innate immunity to determine M. pulmonis numbers in the lung, and early after respiratory infection TLR2 recognition of M. pulmonis triggers initial cytokine responses of host cells.
PubMed 20927103: TLR2 functions as a sensor of oxidation-associated molecular patterns, providing a key link connecting inflammation, oxidative stress, innate immunity and angiogenesis.
PubMed 21439957: TLR1 :: TLR2 dimeric pairs recognize malarial glycosylphosphatidylinositols (GPI) to initiates intracellular signalling and the production of pro-inflammatory cytokines.
PubMed 21454596: TLR2 recognizes Thermus aquaticus extracellular polysacchride, YT-1, and induces the production of cytokines TNF and IL6 in peritoneal macrophages. (Demonstrated in murine model)
PubMed 21482737: TLR2::TLR6 synergistically interacts with TLR9 in lung epithelium to induce rapid pathogen killing, and can be used as a therapeutic target to treat otherwise lethal pneumonia.
PubMed 21512004: TLR2 is activated by gut commensal microbe, Bacteroides fragilis, to establish host-microbial symbiosis by promoting immunological tolerance. (Demonstrated in murine model)
PubMed 21566133: TLR2 and TNFSF11 signalling pathways are modulated by Porphromonas gingivalis to alter the differentiation states of osteoclasts resulting in bacteria-mediated bone loss. (Demonstrated in murine model)
PubMed 21602496: TLR2 is expressed by Muller cells, principal glia of retina, and is responsible for generating robust bactericidal activity against Staphylococcus aureus and contributing to retinal innate defence.
PubMed 21698237: TLR2 is required for rapid inflammasome activation in response to infection by cytosolic bacterial pathogens such as Francisella novicida. (Demonstrated in murine model)
PubMed 21862586: TLR2-driven integration of inducible nitric oxide synthase (iNOS), Wnt-beta-Catenin and NOTCH1 signalling contributes to its capacity to regulate a battery of genes associated with T regulatory cell lineage commitment and towards modulation of defined set of effector functions in macrophages. (Demonstrated in murine model)
PubMed 21873606: TLR2 directly recognizes glycogen, resulting in the activation of immunocytes such as macrophages to enhance the production of nitric oxide and inflammatory cytokines.
PubMed 22096480: TLR2 and TLR4 are crucial for in vivo recognition of Chlamydia pneumoniae. Tlr2/4 double-deficient mice were unable to control pneumonia caused by C. pneumoniae. (Demonstrated in mice)
PubMed 22102818: TLR2 signalling promotes protective vaccine-enhancing Th17 cell responses when cells are stimulated with early secreted antigenic target protein 6 (ESAT-6) expressed by the virulent Mycobacterium tuberculosis strain H37Rv but not by tuberculosis vaccine Bacillus Calmette-Guérin (BCG). (Demonstrated in mice)
PubMed 22174456: TLR2 recognizes Mycobacterium tuberculosis H37Rv cell surface lipoprotein MPT83, which induces the production of TNF, IL6, and IL12B cytokines by macrophages and upregulates macrophage function. (Demonstrated in mouse)
PubMed 22216191: Mycobacterium abscessus glycopeptidolipid (GPL) prevents TLR2-mediate induction of IL8 and DEFB4A in respiratory epithelial cells.
PubMed 25353353: Interaction of filamentous hemagglutinin (FHA) with TLR2 induces an innate immune response against Bordetella pertussis and the TLR2-binding domain of FHA may contribute to immunoprotection against pertussis infection.
PubMed 25456159: Cutaneous bacteria can negatively regulate skin-driven immune responses by inducing Gr1(+)CD11b(+) myeloid-derived suppressor cells via TLR2-6 activation.
PubMed 25531754: Soluble TLR2 (sTLR2) generated by metalloproteinase activation inhibits TLR2-induced cytokine production in THP-1 cell line.
PubMed 25977263: TLR10 is a functional receptor involved in the innate immune response to H. pylori infection and the TLR2/TLR10 heterodimer functions in H. pylori lipopolysaccharide recognition.
PubMed 25955717: Human Cytomegalovirus (HCMV) miR-UL112-3p efficiently targets TLR2 during HCMV infection, resulting in the inhibition of TLR2-mediated NFκB signalling.
PubMed 26610398: H. pylori infection induces the expression and activation of components of NLRP3 inflammasomes in neutrophils and this activation is independent of a functional type IV secretion system, TLR2 and TLR4.
PubMed 26283364: Staphylococcal superantigen-like protein 3 (SSL3) interferes with TLR2 activation at two stages. First by binding to TLR2 and blocking ligand binding and second by interacting with an already formed TLR2-lipopeptide complex, thus preventing TLR heterodimerization and downstream signalling.
PubMed 26310831: PELI3 is involved in endotoxin tolerance and functions as a negative regulator of TLR2/4 signalling.
2017-05-18
DDX60L (Homo sapiens) PubMed 26269178: DDX60L is an important effector protein of the innate immune response against hepatitis C virus.
2017-05-18
IFNG (Homo sapiens) PubMed 20157607: The combined treatment of IFNG with 1,25-dihydroxyvitamin D3 (1,25-D3) synergistically enhances nitric oxide (NO) synthesis and NOS2 expression induced by Mycobacterium tuberculosis (MTB) or by its purified protein derivatives in human monocyte-derived macrophages.
PubMed 20381453: IFNG mediates DUOX2 dual oxidase expression via a STAT-independent signalling pathway and providing insights into a novel IFNG signalling pathway with potential importance for regulation of host defence responses.
PubMed 17981204: IFNG is crucial for immunity against intracellular pathogens and for tumour control and it is produced predominantly by natural killer (NK) and natural killer T (NKT) cells as part of the innate immune response.
PubMed 24012417: IFN gamma creates a primed chromatin environment in macrophages to augment TLR-induced gene transcription.
PubMed 25474109: IFNG interferes with the IL-1/NFKBIZ axis in β-glucan-activated dendritic cells and promotes T cell-mediated immune responses with increased release of IFNG and IL22, and diminished production of IL17A.
PubMed 25732728: Primary γδ T cells provide an early source of IFNG during dengue virus (DV) infection and target DV-infected cells. Monocytes also participate as accessory cells that sense DV infection and amplify the cellular immune response in an IL18-dependent manner.
PubMed 25637949: DEFB103A and RNASE7 are induced in human umbilical endothelial cells (HUVECs) by classical inflammatory cytokines such as: IFNG, IL1B and TNF.
PubMed 26288256: IFNG primes mast cells for enhanced anti-bacterial and pro-inflammatory responses to Staphylococcus aureus, partially mediated by ITGB1.
2017-05-18
TLR3 (Homo sapiens) PubMed 19074283: TLR3-type II IFN signalling cooperates with the RIG-I/MDA5-type I IFN axes for efficient innate antiviral immune responses.
PubMed 19865078: TLR3-dependent antiviral pathway is negatively regulated by activated F2RL1 leading to blunted expression of TLR3/IRF3 driven genes, as well as activation of IRF3 and STAT1.
PubMed 19865078: TLR3, TLR2, or TLR4 cooperate with proteinase-activated receptors (PARs) for activation of nuclear factor-kappaB-dependent signalling in mucosal epithelial cell lines.
PubMed 20019748: TLR3-induced proapoptotic signalling involves TICAM1 (TRIF)-dependent activation of CASP8 and is under the control of inhibitor of apoptosis proteins (IAPs) in melanoma cells.
PubMed 11607032: TLR3 is activated by poly(I:C) and this induces cytokine production through a signalling pathway dependent on MyD88.
PubMed 14982987: TLR3-mediated activation of NF-kappaB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter 1 (TICAM1) inducing IFN-beta.
PubMed 20861016: TLR3 dimerizes when it binds dsRNA and this is essential for ligand binding. Although the three TLR3 contact sites individually interact weakly with their binding partners, together they form a high affinity ligand-receptor complex.
PubMed 21220319: TLR3 deletion dramatically enhanced the development of elastic lamina damage after collar-induced injury, indicating that TLR3 signalling plays a protective role in arterial vessel wall.
PubMed 21367858: TLR3 activation by Poly(I:C) in the endothelial cells induces Poly(I:C) dose- and time-dependent cell apoptosis. Specifically, TLR3 stimulation triggered the signalling of both extrinsic and intrinsic apoptotic pathways.
PubMed 21402738: TLR3 requires proteolytic processing in endolysosome by asparagine endopeptidase and cathepsin in the endolysosome to initiate signalling in response to DNA. (Demonstrated in murine model)
PubMed 21498625: TLR3 expression is inducible by LPS via TLR4-MYD88-IRAK-TRAF6-NFKB dependent signalling pathway.
PubMed 21695051: TLR3 is necessary to establish an antiviral state in hepatocytes infected with hepatitis C Virus. HCV envelope proteins counteract the antiviral host defence by inhibiting the expression of TLR3.
PubMed 22016778: TLR3 signalling is enhanced by the presence of viral double-strand RNA-binding proteins.
PubMed 22072781: TLR3-TICAM1-mediated signalling pathway plays an essential role in the anti-viral response against poliovirus infection. (Demonstrated in mice)
PubMed 22262694: TLR3 is constitutively expressed in spermatogonia and spermatocytes, and has the ability to activate anti-viral responses. (Demonstrated in mice)
PubMed 22421964: Upon engagement with its ligand, dsRNA, TLR3 possesses the ability to recruit CASP8 and RIPK1 to induce apoptosis.
PubMed 22754655: Activation of TLR3 with poly(I:C) mediates antiviral immunity that diminishes coronavirus production in macrophages. (Demonstrated in mice)
PubMed 22570612: Upregulation of TLR3 in intestinal epithelia during infancy may contribute to age-dependent susceptibility to rotavirus infection. (Demonstrated in mice)
PubMed 22986631: TLR3 activation differentially regulates phagocytosis of bacteria and apoptotic neutrophils by peritoneal macrophages. (Demonstrated in mice)
PubMed 23035017: TLR3 is more efficiently activated by high molecular mass than by low molecular weight poly(I:C).
PubMed 25452586: TLR3-mediated antibody response to Chikungunya virus plays a key role in its infection, replication and pathology.
PubMed 25641411: Intracellular/endocytic TLR3 interacts with SCARF 1 in the presence of Poly I:C to boost TLR3-mediated inflammatory signalling and stimulate cytokine production in macrophages.
PubMed 25880109: Signalling through both DDX58 and TLR3 is important for interferon induction by influenza A virus in alveolar epithelial cells.
PubMed 26296370: Bluetongue virus activates TLR3/interferons signalling pathway resulting in the inhibition of human immunodeficiency virus in macrophages.
2017-05-18
NFKBIZ (Homo sapiens) PubMed 16513645: Inhibits the DNA binding of RELA and NFKB1
PubMed 19783680: A key regulator of IL-6 production in human monocytes and plays an important role in both TLR and NOD-like receptor ligand induced inflammation
PubMed 25474109: IFNG interferes with the IL-1/NFKBIZ axis in β-glucan-activated dendritic cells and promotes T cell-mediated immune responses with increased release of IFNG and IL22, and diminished production of IL17A.
PubMed 26287468: TET2 selectively mediates active repression of IL6 transcription via NFKBIZ and HDAC2 during inflammation resolution in innate myeloid cells, including dendritic cells and macrophages.
2017-05-18
RELA (Homo sapiens) PubMed 11980335: RELA, NF-kappaB p65 subunit, is involved in the transcription regulation of many genes including those genes involved in apoptosis, response to stress and inflammation.
PubMed 21209118: RELA is a subunit of NFKB and is not essential for virus-stimulated IFNB expression, instead, RELA sustains autocrine IFNB signalling prior to infection. The absence of RELA causes significant delays in IFNB induction and consequently defective secondary antiviral gene expression. RELA maintains autocrine IFNB signalling in uninfected cells, facilitates inflammatory and adaptive immune responses following infection, and promotes infected cell survival during this process.
PubMed 21216972: RELA is critical for pulmonary host defence during Streptococcus pneumoniae pneumonia in alveolar macrophages. During pneumococcal pneumonia, only the earliest induction of cytokines depends on transcription regulated by RELA in myeloid cells, and this transcriptional activity contributes to effective immunity. (Demonstrated in murine model)
PubMed 21419662: RELA is required for IL17A production in T cell in response to bacterial infection. RELA deficient T cells resulted in a diminished innate immune response to E. coli infection. (Demonstrated in murine model)
PubMed 23271966: A RELA isoform, p43, lacks the transactivation domain but is still able to potentiate anti-viral innate immunity.
PubMed 23994473: During the transcriptional response to Sendai virus infection, POLR2F(RNA Pol II) is recruited by IRF3 and NFκB to control virus induced gene activation.
PubMed 25520509: Paramyxoviruses trigger the DNA-damage response, a pathway required for RPS6KA5 activation of phospho Ser 276 RELA formation to trigger the IRF7-DDX58 amplification loop necessary for mucosal interferon production.
PubMed 26055519: Human papillomaviruses impair the acetylation of NFκB/RelA K310 in keratinocytes by augmenting the expression of interferon-related developmental regulator 1 (IFRD1) in an EGFR-dependent manner.
PubMed 26642243: Haploinsufficiency of A20 (HA20) is caused by high-penetrance loss-of-function germline mutations in TNFAIP3 with increased degradation of NFKBIA, nuclear translocation of RELA, increased expression of NFκB mediated proinflammatory cytokines, and defective deubiquitinating activity.
PubMed 26296289: MIR223 regulates macrophage function by modulating cytokine production and NF-κB activation through inhibition of RELA phosphorylation and nuclear translocation.
2017-05-18