Mucosal Immunol. 2009 Sep 9. [Epub ahead of print]
CCR2-dependent intraepithelial lymphocytes mediate inflammatory gut pathology during Toxoplasma gondii infection
Egan C, Craven M, Leng J, Mack M, Simpson K, Denkers E.
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Mice of the C57BL/6 strain develop acute ileal inflammation after infection with the protozoan parasite Toxoplasma gondii. This pathology resembles many key features of human Crohn's disease, including a Th1 cytokine profile with high levels of interferon gamma (IFN-gamma), interleukin 12 (IL)-12, and tumor necrosis factor alpha (TNF)-alpha, presence of pathogenic CD4(+) T cells, and infiltration of gut flora into inflammed tissue. Using CCR2(-/-) mice, we identify a role for this chemokine receptor in the pathogenesis of inflammatory pathology during T. gondii infection. Lack of chemokine (C-C motif) receptor 2 (CCR2) was associated with low levels of CD103(+) T lymphocytes in the intraepithelial compartment, Peyer's patch, and lamina propria relative to wild-type animals. Adoptive transfer of wild-type, but not IFN-gamma(-/-), intraepithelial T lymphocytes converted CCR2 knockout mice from a resistant to susceptible phenotype with respect to parasite-triggered inflammatory gut pathology. These results for the first time show a role for intraepithelial T lymphocytes in pathogenesis of ileitis triggered by a microbial pathogen.Mucosal Immunology advance online publication 9 September 2009. doi:10.1038/mi.2009.105.
PMID: 19741601 [PubMed - as supplied by publisher]