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Published online before print January 25, 2008

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(Journal of Leukocyte Biology. 2008;83:833-842.)
© 2008 by Society for Leukocyte Biology

Aging in the absence of TLR2 is associated with reduced IFN- responses in the large intestine and increased severity of induced colitis

Eric J. Albert^* and Jean S. Marshall^*,,1

Dalhousie Inflammation Group, Departments of Microbiology and Immunology, and
^* Pathology, Dalhousie University, Halifax, Nova Scotia, Canada

¹ Correspondence: Dalhousie University, Dept. of Microbiology & Immunology, Sir Charles Tupper Medical Building, Room 7C, 5850 College St., Halifax, Nova Scotia, Canada, B3H1X5. E-mail: jean.marshall{at}dal.ca

ABSTRACT

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- 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- 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.

Key Words: mucosal immunology • rodent • inflammation • Toll-like receptors • Trefoil factors • inflammatory bowel disease