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Gnotobiotic Toll-Like Receptor 5 Deficient Mice Lack Spontaneous Colitis and Metabolic Syndrome
Sa1770
metabolic syndrome and colitis, respectively. Methods: Embryo transplant was performed to generate gnotobiotic mice heterozygous-null for TLR5, which were then bred in gnotobiotic housing to attain gnotobiotic TLR5KO mice and WT littermates. Gnotobiotic 10-12 week old wild type (WT) and TLR5-deficient (TLR5KO) mice were euthanized in sterile conditions and analyzed for various metabolic and inflammatory parameters including blood glucose, body and organ weights, tissue myeloperoxidase (MPO) and histology. To verify that the gnotobiotic mice lacked TLR agonists, the ability of cecal contents to elicit an innate immune response (i.e. cytokines) in conventional WT mice was ascertained. Cytokines were analyzed both in serum and ex vivo colon and small intestinal cultures. Serum and liver lipid content were also analyzed as was gene expression in the colon and liver. Metabolic function was assayed via evaluation of serum glucose, insulin and leptin. Results: WT and TLR5KO mice were confirmed to lack detectable TLR agonists in their feces/cecal contents as these failed to elicit an immune response in conventional mice. Careful comparison of gnotobiotic WT and TLR5KO for a variety of parameters associated with both colitis and metabolic syndrome found no phenotypic distinctions between these groups of mice. Conclusion: Gnotobiotic mice lack functionally relevant levels of TLR agonists in the gut indicating TLR activation in the gut is driven by commensal bacteria rather than dietary or host-derived agonists. While conventional TLR5KO are prone to both colitis and metabolic syndrome, rederivation of these mice to the gnotobiotic state makes them phenotypically indistinguishable from WT gnotobiotic mice. These findings confirm that the previously described phenotypes of TLR5KO mice result from loss of recognition of intestinal bacteria and are in accord with the notion that TLR5KO mice are prone to developing gut inflammation due to an inability to manage the commensal gut microbiota.
AGA Abstracts
Amylin and Leptin Signaling Converge on Leptin Receptor Neurons of the Nucleus of the Solitary Tract and the Lateral Parabrachial Nucleus in the Murine Brain Michael Rajala, Christa Patterson, Martin Myers The inherent redundancies in the brain circuitry regulating food intake and body weight have made single hormone target therapies for weight loss relatively ineffective. Exogenous leptin decreases food intake and body weight in rodents through central activation of the signaling form of the leptin receptor (LepRb); however, leptin treatment of obese human patients is ineffective in producing weight loss. Employing a multi-target approach, recent results have demonstrated that concurrent treatment with amylin, a nutritionally regulated pancreatic beta-cell hormone, and leptin can synergistically reduce food intake and promote weight loss in both rodents and humans. To determine whether amylin and leptin converge on and activate similar sets of neurons, we examined activation of cFos (a maker of neuronal activity) following peripheral amylin administration in mice expressing yellow fluorescent protein only in LepRb neurons (LepRb-YFP). Consistent with known amylin targets, cFos was induced in the area postrema (AP), the established primary entry point for the central satiety action of amylin. Although the AP is devoid of LepRb neurons, amylin also promoted cFos in the nucleus of the solitary tract (NTS)(a known target of AP amylin-sensing neurons), lateral parabrachial nucleus (lPBN), central nucleus of the amygdala (CeA) and several hypothalamic nuclei (VMH, DMH, LHA); many of these areas contain substantial number of LepRb neurons. Indeed, amylin induced cFos activation in a significant population of LepRb neurons within the medial NTS and lPBN, suggesting that these hindbrain LepRb neurons represent a point of convergence for amylin and leptin action. In order to determine if amylin activates other neurons that lie in direct contact with LepRb neurons, we utilized a mouse model (LepRb-WGA) in which wheat germ agglutinin (WGA) identifies the neurons in synaptic contact with LepRb neurons. Amylin administration promoted cFos activation in WGA-containing neurons of the medial NTS, revealing a second point of convergence of leptin and amylin action in the hindbrain. Together, these results reveal multiple points of convergence between amylin and leptin signaling in the hindbrain, specifically NTS and LPBN LepRb neurons along with other NTS neurons that are innervated by LepRb neurons and activated by amylin. Current studies are assessing cFos activation in LepRb neurons following both leptin and amylin administration in LepRb-YFP mice to test the possibility that leptin and amylin regulate these neurons synergistically.
Sa1773 Antibiotics Induced Commensal Flora Disruption Favours Escherichia coli AIEC (LF82) Colonization in Wild Type and NOD2 Knock-out Mice Maryline Drouet, Cécile Vignal, Elisabeth Singer, Luc Dubreuil, Pierre Desreumaux, Christel Neut Ileal lesions of Crohn's disease (CD) patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC). NOD2 gene mutations are risk factors for ileal CD and are associated with an abnormal AIEC-induced immune response. AIM: since innate immune system and commensal microbial colonization are critical to maintain intestinal barrier integrity, we evaluated the impact of commensal microbial colonization disruption induced by short term antibiotic treatment on AIEC LF82 colonization and translocation in wild type (WT) and NOD2 knock-out mice (NOD2KO). MATERIALS: Disruption of commensal microbial colonization was induced by a 3 days antibiotic treatment (gentamicin 3 mg/kg/d and vancomycin 40 mg/kg/d) administered by oral gavage in NOD2KO (n=75) mice and their C57/Bl6 WT wild type littermates (n=75). At day 3, mice were infected with 109 CFU AIEC once a day for 2 days. Non infected and infected mice without antibiotic treatment were used as controls (n=6 per group). Animals were sacrificed at day 1 (n=32), day 30 (n=48) and day 60 (n=48) after AIEC administration. Ileum, colon and mesenteric lymph nodes were sampled for 1) AIEC quantification in ileal and colonic tissues (detection rate 104cfu/ g), 2) bacterial translocation in mesenteric lymph nodes (detection rate 102cfu/g), and 3) evaluation of histological abnormalities and intestinal inflammation. RESULTS: Without antibiotic treatment, AIEC was not able to colonize WT and NOD2KO mice at day 1, 30 and 60 and did not induce bacterial translocation, histologic ileal and colonic abnormalities and/or inflammation. Compared to control animals, commensal microbial disruption induced by antibiotics led to a significant increase of ileal and colonic adherent AIEC in both NOD2KO mice (respectively 6.23log±0.52 cfu/g ileum and 6.65log±0.27 cfu/g colon) and WT animals (respectively 7.61log±0.27 cfu/g ileum and 8.8log ±0.31 cfu/g colon) at day 1. Persistent AIEC colonization was still observed at day 30 in the ileum and not the colon of both NOD2KO mice (5.5log±0.71 cfu/g ileum) and WT animals (5.25log ±0.28 cfu/g ileum), disappearing at day 60. Mesenteric translocation of AIEC was observed at day 1 in both NOD2KO mice (2.4log±0.31) and WT animals (3log±0.07) and was maintained until day 30 only in NOD2KO mice (3.46log±0.79). No histologic ileal and colonic abnormalities and/or inflammation were observed in NOD2KO mice and their WT littermates treated with antibiotics and infected with AIEC. CONCLUSION: WT and NOD2KO mice were spontaneously resistant to AIEC infection. Sustained AIEC colonization in ileal tissues of mice was induced by commensal flora disruption promoted by short term antibiotic treatment, independently of NOD2 expression. In contrast, commensal flora disruption by antibiotics induced a long term AIEC bacterial translocation in a NOD2 dependent manner.
Sa1771 Characterization of Receptors and Signaling Pathways Coupled to Umami Taste in Enteroendocrine Cells Vanitha Bala, Sunila Mahavadi, Vijay Lyall, Karnam S. Murthy, John R. Grider Recent studies demonstrated that a subset of chemosensing receptors and signaling molecules in the gastrointestinal mucosa are similar to the gustatory signals in the oral cavity. Activation of these receptors by various tastants is involved in the regulation of food intake, motility, and secretion involving interplay between the enteroendocrine cells and visceral sensory neurons. Functional sweet and bitter taste receptors have been identified in the gut mucosa and their activation via T1R2/T1R3- and T2R-coupled Gα gustducin signaling, respectively, underlie the secretion of glucagon-like peptide-1 (GLP-1) and cholecystokinin. Umami, a fifth sense of taste, perceived in the oral cavity by amino acids such as glutamate, is shown to activate several G protein coupled receptors including metabotropic glutamate receptors as well as Gαgustducin-coupled T1R1/T1R3 heterodimer receptors. Activation of the latter causes stimulation of βγ-dependent PLC-β2 activity, IP3-dependent Ca2+ release and Ca2+dependent nonselective cation channel TRPM5 function. AIM: To determine the expression of T1R1/T1R3 receptors and the related signaling molecules, and their colocalization with various gut peptides in enteroendocrine STC-1 cells. METHODS: STC-1 cells were obtained from ATCC and maintained in culture. Expression of T1R1, T1R3, Gα gustuducin, PLCβ2 and TRPM5 was examined by RT-PCR, western blot and immunohistochemistry (IHC). Colocalization of GLP-1, peptide YY (PYY), and neurotensin (NT) with umami taste-specific T1R1 was examined by IHC. Activation of PLC-β2 in response to umami ligand, monosodium glutamate (MSG, 10 mM) was examined in cells labeled with [3H]myo-inositol. Stimulation of ERK1/2 activity, and GLP-1 and PYY release in response to MSG was measured by immunokinase assay and ELISA. RESULTS: RT-PCR, western blot and IHC studies showed the expression of T1R1, T1R3, Gα gustducin, PLC-β2 and TRPM5 in STC-1 cells. Immunohistochemistry revealed 82% colocalization of T1R1 with GLP-1, 80% with T1R3, 22% with PYY and 56% with NT. Treatment of cells with MSG caused stimulation of PLC-β2 and ERK1/2 activity and induced release of GLP-1 and PYY. The PI-PLC inhibitor U73122 reduced the effect of MSG on GLP-1 and PYY release. CONCLUSION. STC-1 cells express Gα gustducin-coupled T1R1/T1R3 receptors and in some cases contain GLP-1, PYY or NT. Activation of these receptors with the umami ligand causes stimulation of PLC-β2 and ERK1/ 2 activity, and GLP-1 and PYY release. Further studies identifying the luminal chemosensing factors that regulate the secretion of gut peptides from the enteroendocrine cells will facilitate the development of therapeutic agents that target these cells to regulate gastrointestinal function.
Sa1774 Defective Macrophage Function in Crohn's Disease: Role of Alternatively Activated Macrophages in Inflammation Christos Karaiskos, Barry N. Hudspith, Tim Elliott, Neil B. Rayment, Vanessa Avgousti, Jonathan Brostoff, Jeremy D. Sanderson The aetiology of Crohn's disease (CD) involves a genetically determined dysregulated immune response to commensal intestinal microflora. In CD, viable E.coli are found within lamina propria macrophages (MΦs) and using In Vitro models we have shown that E.coli intracellular survival is prolonged in CD-derived ΜΦs. It is now recognised that different MΦ subpopulations exist, M1 cells are inflammatory cells, M2a cells are involved in tissue repair and M2c are regulatory cells that limit inflammation. However, the role these different MΦs play in this abnormal handling of bacteria in CD is unclear. The aim of this study was to examine In Vitro M1 and M2 MΦ maturation in CD patients compared to healthy individuals and how these cells respond to challenge with CD-derived E.coli. To do this we monitored MΦ morphology, surface markers, cytokine production and intracellular bacterial survival. Peripheral blood monocytes were isolated from CD patients and healthy controls and treated with cytokines to generate distinct MΦ subpopulations: IFNγ for M1, IL4/IL13 for M2a and IL10 for M2c. MΦ morphology was assessed by H&E staining and surface marker expression of CD14, CD16 and CD33, chemokine receptor CCR2, scavenger receptor CD163, co stimulatory molecule CD40 and mannose receptor CD206 using flow cytometry. IL10 and TNFα production were measured by ELISA and intracellular E.coli survival was measured
Sa1772 Gnotobiotic Toll-Like Receptor 5 Deficient Mice Lack Spontaneous Colitis and Metabolic Syndrome Matam Vijay-Kumar, Jesse D. Aitken, Yueju Su, Gayathri Srinivasan, Frederic A. Carvalho, Andrew T. Gewirtz Introduction: Toll Like Receptor 5 (TLR5), an innate immune receptor expressed basolaterally by epithelial cells in multiple tissues, detects bacterial flagellin and serves to monitor and maintain the barrier between the lumen and host tissue. TLR5's function is especially important in the gut, where it works in concert with other pattern recognition receptors to protect against pathogenic and opportunistic bacteria. Mice lacking TLR5 (TLR5KO) are predisposed to developing spontaneous low-grade and robust inflammation resulting in
AGA Abstracts
S-324
metabolic syndrome and colitis, respectively. Methods: Embryo transplant was performed to generate gnotobiotic mice heterozygous-null for TLR5, which were then bred in gnotobiotic housing to attain gnotobiotic TLR5KO mice and WT littermates. Gnotobiotic 10-12 week old wild type (WT) and TLR5-deficient (TLR5KO) mice were euthanized in sterile conditions and analyzed for various metabolic and inflammatory parameters including blood glucose, body and organ weights, tissue myeloperoxidase (MPO) and histology. To verify that the gnotobiotic mice lacked TLR agonists, the ability of cecal contents to elicit an innate immune response (i.e. cytokines) in conventional WT mice was ascertained. Cytokines were analyzed both in serum and ex vivo colon and small intestinal cultures. Serum and liver lipid content were also analyzed as was gene expression in the colon and liver. Metabolic function was assayed via evaluation of serum glucose, insulin and leptin. Results: WT and TLR5KO mice were confirmed to lack detectable TLR agonists in their feces/cecal contents as these failed to elicit an immune response in conventional mice. Careful comparison of gnotobiotic WT and TLR5KO for a variety of parameters associated with both colitis and metabolic syndrome found no phenotypic distinctions between these groups of mice. Conclusion: Gnotobiotic mice lack functionally relevant levels of TLR agonists in the gut indicating TLR activation in the gut is driven by commensal bacteria rather than dietary or host-derived agonists. While conventional TLR5KO are prone to both colitis and metabolic syndrome, rederivation of these mice to the gnotobiotic state makes them phenotypically indistinguishable from WT gnotobiotic mice. These findings confirm that the previously described phenotypes of TLR5KO mice result from loss of recognition of intestinal bacteria and are in accord with the notion that TLR5KO mice are prone to developing gut inflammation due to an inability to manage the commensal gut microbiota.
AGA Abstracts
Amylin and Leptin Signaling Converge on Leptin Receptor Neurons of the Nucleus of the Solitary Tract and the Lateral Parabrachial Nucleus in the Murine Brain Michael Rajala, Christa Patterson, Martin Myers The inherent redundancies in the brain circuitry regulating food intake and body weight have made single hormone target therapies for weight loss relatively ineffective. Exogenous leptin decreases food intake and body weight in rodents through central activation of the signaling form of the leptin receptor (LepRb); however, leptin treatment of obese human patients is ineffective in producing weight loss. Employing a multi-target approach, recent results have demonstrated that concurrent treatment with amylin, a nutritionally regulated pancreatic beta-cell hormone, and leptin can synergistically reduce food intake and promote weight loss in both rodents and humans. To determine whether amylin and leptin converge on and activate similar sets of neurons, we examined activation of cFos (a maker of neuronal activity) following peripheral amylin administration in mice expressing yellow fluorescent protein only in LepRb neurons (LepRb-YFP). Consistent with known amylin targets, cFos was induced in the area postrema (AP), the established primary entry point for the central satiety action of amylin. Although the AP is devoid of LepRb neurons, amylin also promoted cFos in the nucleus of the solitary tract (NTS)(a known target of AP amylin-sensing neurons), lateral parabrachial nucleus (lPBN), central nucleus of the amygdala (CeA) and several hypothalamic nuclei (VMH, DMH, LHA); many of these areas contain substantial number of LepRb neurons. Indeed, amylin induced cFos activation in a significant population of LepRb neurons within the medial NTS and lPBN, suggesting that these hindbrain LepRb neurons represent a point of convergence for amylin and leptin action. In order to determine if amylin activates other neurons that lie in direct contact with LepRb neurons, we utilized a mouse model (LepRb-WGA) in which wheat germ agglutinin (WGA) identifies the neurons in synaptic contact with LepRb neurons. Amylin administration promoted cFos activation in WGA-containing neurons of the medial NTS, revealing a second point of convergence of leptin and amylin action in the hindbrain. Together, these results reveal multiple points of convergence between amylin and leptin signaling in the hindbrain, specifically NTS and LPBN LepRb neurons along with other NTS neurons that are innervated by LepRb neurons and activated by amylin. Current studies are assessing cFos activation in LepRb neurons following both leptin and amylin administration in LepRb-YFP mice to test the possibility that leptin and amylin regulate these neurons synergistically.
Sa1773 Antibiotics Induced Commensal Flora Disruption Favours Escherichia coli AIEC (LF82) Colonization in Wild Type and NOD2 Knock-out Mice Maryline Drouet, Cécile Vignal, Elisabeth Singer, Luc Dubreuil, Pierre Desreumaux, Christel Neut Ileal lesions of Crohn's disease (CD) patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC). NOD2 gene mutations are risk factors for ileal CD and are associated with an abnormal AIEC-induced immune response. AIM: since innate immune system and commensal microbial colonization are critical to maintain intestinal barrier integrity, we evaluated the impact of commensal microbial colonization disruption induced by short term antibiotic treatment on AIEC LF82 colonization and translocation in wild type (WT) and NOD2 knock-out mice (NOD2KO). MATERIALS: Disruption of commensal microbial colonization was induced by a 3 days antibiotic treatment (gentamicin 3 mg/kg/d and vancomycin 40 mg/kg/d) administered by oral gavage in NOD2KO (n=75) mice and their C57/Bl6 WT wild type littermates (n=75). At day 3, mice were infected with 109 CFU AIEC once a day for 2 days. Non infected and infected mice without antibiotic treatment were used as controls (n=6 per group). Animals were sacrificed at day 1 (n=32), day 30 (n=48) and day 60 (n=48) after AIEC administration. Ileum, colon and mesenteric lymph nodes were sampled for 1) AIEC quantification in ileal and colonic tissues (detection rate 104cfu/ g), 2) bacterial translocation in mesenteric lymph nodes (detection rate 102cfu/g), and 3) evaluation of histological abnormalities and intestinal inflammation. RESULTS: Without antibiotic treatment, AIEC was not able to colonize WT and NOD2KO mice at day 1, 30 and 60 and did not induce bacterial translocation, histologic ileal and colonic abnormalities and/or inflammation. Compared to control animals, commensal microbial disruption induced by antibiotics led to a significant increase of ileal and colonic adherent AIEC in both NOD2KO mice (respectively 6.23log±0.52 cfu/g ileum and 6.65log±0.27 cfu/g colon) and WT animals (respectively 7.61log±0.27 cfu/g ileum and 8.8log ±0.31 cfu/g colon) at day 1. Persistent AIEC colonization was still observed at day 30 in the ileum and not the colon of both NOD2KO mice (5.5log±0.71 cfu/g ileum) and WT animals (5.25log ±0.28 cfu/g ileum), disappearing at day 60. Mesenteric translocation of AIEC was observed at day 1 in both NOD2KO mice (2.4log±0.31) and WT animals (3log±0.07) and was maintained until day 30 only in NOD2KO mice (3.46log±0.79). No histologic ileal and colonic abnormalities and/or inflammation were observed in NOD2KO mice and their WT littermates treated with antibiotics and infected with AIEC. CONCLUSION: WT and NOD2KO mice were spontaneously resistant to AIEC infection. Sustained AIEC colonization in ileal tissues of mice was induced by commensal flora disruption promoted by short term antibiotic treatment, independently of NOD2 expression. In contrast, commensal flora disruption by antibiotics induced a long term AIEC bacterial translocation in a NOD2 dependent manner.
Sa1771 Characterization of Receptors and Signaling Pathways Coupled to Umami Taste in Enteroendocrine Cells Vanitha Bala, Sunila Mahavadi, Vijay Lyall, Karnam S. Murthy, John R. Grider Recent studies demonstrated that a subset of chemosensing receptors and signaling molecules in the gastrointestinal mucosa are similar to the gustatory signals in the oral cavity. Activation of these receptors by various tastants is involved in the regulation of food intake, motility, and secretion involving interplay between the enteroendocrine cells and visceral sensory neurons. Functional sweet and bitter taste receptors have been identified in the gut mucosa and their activation via T1R2/T1R3- and T2R-coupled Gα gustducin signaling, respectively, underlie the secretion of glucagon-like peptide-1 (GLP-1) and cholecystokinin. Umami, a fifth sense of taste, perceived in the oral cavity by amino acids such as glutamate, is shown to activate several G protein coupled receptors including metabotropic glutamate receptors as well as Gαgustducin-coupled T1R1/T1R3 heterodimer receptors. Activation of the latter causes stimulation of βγ-dependent PLC-β2 activity, IP3-dependent Ca2+ release and Ca2+dependent nonselective cation channel TRPM5 function. AIM: To determine the expression of T1R1/T1R3 receptors and the related signaling molecules, and their colocalization with various gut peptides in enteroendocrine STC-1 cells. METHODS: STC-1 cells were obtained from ATCC and maintained in culture. Expression of T1R1, T1R3, Gα gustuducin, PLCβ2 and TRPM5 was examined by RT-PCR, western blot and immunohistochemistry (IHC). Colocalization of GLP-1, peptide YY (PYY), and neurotensin (NT) with umami taste-specific T1R1 was examined by IHC. Activation of PLC-β2 in response to umami ligand, monosodium glutamate (MSG, 10 mM) was examined in cells labeled with [3H]myo-inositol. Stimulation of ERK1/2 activity, and GLP-1 and PYY release in response to MSG was measured by immunokinase assay and ELISA. RESULTS: RT-PCR, western blot and IHC studies showed the expression of T1R1, T1R3, Gα gustducin, PLC-β2 and TRPM5 in STC-1 cells. Immunohistochemistry revealed 82% colocalization of T1R1 with GLP-1, 80% with T1R3, 22% with PYY and 56% with NT. Treatment of cells with MSG caused stimulation of PLC-β2 and ERK1/2 activity and induced release of GLP-1 and PYY. The PI-PLC inhibitor U73122 reduced the effect of MSG on GLP-1 and PYY release. CONCLUSION. STC-1 cells express Gα gustducin-coupled T1R1/T1R3 receptors and in some cases contain GLP-1, PYY or NT. Activation of these receptors with the umami ligand causes stimulation of PLC-β2 and ERK1/ 2 activity, and GLP-1 and PYY release. Further studies identifying the luminal chemosensing factors that regulate the secretion of gut peptides from the enteroendocrine cells will facilitate the development of therapeutic agents that target these cells to regulate gastrointestinal function.
Sa1774 Defective Macrophage Function in Crohn's Disease: Role of Alternatively Activated Macrophages in Inflammation Christos Karaiskos, Barry N. Hudspith, Tim Elliott, Neil B. Rayment, Vanessa Avgousti, Jonathan Brostoff, Jeremy D. Sanderson The aetiology of Crohn's disease (CD) involves a genetically determined dysregulated immune response to commensal intestinal microflora. In CD, viable E.coli are found within lamina propria macrophages (MΦs) and using In Vitro models we have shown that E.coli intracellular survival is prolonged in CD-derived ΜΦs. It is now recognised that different MΦ subpopulations exist, M1 cells are inflammatory cells, M2a cells are involved in tissue repair and M2c are regulatory cells that limit inflammation. However, the role these different MΦs play in this abnormal handling of bacteria in CD is unclear. The aim of this study was to examine In Vitro M1 and M2 MΦ maturation in CD patients compared to healthy individuals and how these cells respond to challenge with CD-derived E.coli. To do this we monitored MΦ morphology, surface markers, cytokine production and intracellular bacterial survival. Peripheral blood monocytes were isolated from CD patients and healthy controls and treated with cytokines to generate distinct MΦ subpopulations: IFNγ for M1, IL4/IL13 for M2a and IL10 for M2c. MΦ morphology was assessed by H&E staining and surface marker expression of CD14, CD16 and CD33, chemokine receptor CCR2, scavenger receptor CD163, co stimulatory molecule CD40 and mannose receptor CD206 using flow cytometry. IL10 and TNFα production were measured by ELISA and intracellular E.coli survival was measured
Sa1772 Gnotobiotic Toll-Like Receptor 5 Deficient Mice Lack Spontaneous Colitis and Metabolic Syndrome Matam Vijay-Kumar, Jesse D. Aitken, Yueju Su, Gayathri Srinivasan, Frederic A. Carvalho, Andrew T. Gewirtz Introduction: Toll Like Receptor 5 (TLR5), an innate immune receptor expressed basolaterally by epithelial cells in multiple tissues, detects bacterial flagellin and serves to monitor and maintain the barrier between the lumen and host tissue. TLR5's function is especially important in the gut, where it works in concert with other pattern recognition receptors to protect against pathogenic and opportunistic bacteria. Mice lacking TLR5 (TLR5KO) are predisposed to developing spontaneous low-grade and robust inflammation resulting in
AGA Abstracts
S-324