Genetic background of IL-10(-/-) mice alters host-pathogen interactions with Campylobacter jejuni and influences disease phenotype |
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Authors: | Mansfield L S Patterson J S Fierro B R Murphy A J Rathinam V A Kopper J J Barbu N I Onifade T J Bell J A |
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Affiliation: | Comparative Enteric Diseases Laboratory, Michigan State University, East Lansing, MI 48824, USA. mansfie4@cvm.msu.edu |
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Abstract: | We hypothesized that particular genetic backgrounds enhance rates of colonization, increase severity of enteritis, and allow for extraintestinal spread when inbred IL-10(-/-) mice are infected with pathogenic C. jejuni. Campylobacter jejuni stably colonized C57BL/6 and NOD mice, while congenic strains lacking IL-10 developed typhlocolitis following colonization that mimicked human campylobacteriosis. However, IL-10 deficiency alone was not necessary for the presence of C. jejuni in extraintestinal sites. C3H/HeJ tlr4(-/-) mice that specifically express the Cdcs1 allele showed colonization and limited extraintestinal spread without enteritis implicating this interval in the clinical presentation of C. jejuni infection. Furthermore, when the IL-10 gene is inactivated as in C3Bir tlr4(-/-) IL-10(-/-) mice, enteritis and intensive extraintestinal spread were observed, suggesting that clinical presentations of C. jejuni infection are controlled by a complex interplay of factors. These data demonstrate that lack of IL-10 had a greater effect on C. jejuni induced colitis than other immune elements such as TLR4 (C3H/HeJ, C3Bir IL-10(-/-)), MHC H-2g7, diabetogenic genes, and CTLA-4 (NOD) and that host genetic background is in part responsible for disease phenotype. C3Bir IL-10(-/-) mice where Cdcs1 impairs gut barrier function provide a new murine model of C. jejuni and can serve as surrogates for immunocompromised patients with extraintestinal spread. |
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Keywords: | Campylobacter jejuni Enteritis Murine disease model IL-10 Toll-like receptor 4 Cytokine deficiency-induced colitis susceptibility 1 (Cdcs1) allele Inflammatory bowel disease |
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