Aging in the absence of TLR2 is associated with reduced IFN-gamma responses in the large intestine and increased severity of induced colitis.
Age-associated changes in immune function and their implications for intestinal inflammation are poorly understood. Defects in innate immunity have been shown to enhance intestinal inflammation and have been demonstrated upon aging. This study aimed to determine the consequences of aging in the presence and absence of TLR2 on intestinal inflammation. Young and aged (>60 weeks), control C57Bl/6 and TLR2-deficient (TLR2(-/-)) mice were examined. The cecum and mid-colon were analyzed for tissue damage, cytokine profiles, and trefoil factor 3 (TFF3) expression at baseline or after 5 days of treatment with dextran sodium sulfate (DSS) and 5 or 13 days recovery. Untreated, aged TLR2(-/-) mice had no significant intestinal inflammation but had reduced colonic IFN-gamma and IL-10 compared with younger mice. Aged TLR2(-/-) mice developed more severe colitis than other groups, as indicated by histological examination and overall weight loss. There were significant increases in colonic IFN-gamma following DSS treatment in young but not in aged mice. TFF3 was substantially reduced in the cecum and increased in the colon of aged but not younger TLR2(-/-) mice following DSS treatment. These results demonstrate that even upon aging, TLR2-deficient animals did not develop intestinal disease. However, they failed to respond appropriately to an inflammatory insult, and the consequences of this were most severe in aged animals. Cytokine and TFF3 changes associated with aging may contribute to more severe intestinal inflammation.
Albert
Eric J
EJ
Dalhousie Inflamation Group, Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Marshall
Jean S
JS
D000375:Aging / Q000502:physiology*; D000818:Animals; D002432:Cecum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D003106:Colon / Q000187:drug effects / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D016264:Dextran Sulfate / Q000633:toxicity; D020022:Genetic Predisposition to Disease; D007371:Interferon-gamma / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051195:Toll-Like Receptor 2 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D007371:Interferon-gamma; D016264:Dextran Sulfate