Contrasting immune responses mediate Campylobacter jejuni-induced colitis and autoimmunity.
Campylobacter jejuni is a leading cause of foodborne enteritis that has been linked to the autoimmune neuropathy, Guillain Barré syndrome (GBS). C57BL/6 interleukin (IL)-10(+/+) and congenic IL-10(-/-) mice serve as C. jejuni colonization and colitis models, respectively, but a mouse model for GBS is lacking. We demonstrate that IL-10(-/-) mice infected with a C. jejuni colitogenic human isolate had significantly upregulated type 1 and 17 but not type 2 cytokines in the colon coincident with infiltration of phagocytes, T cells and innate lymphoid cells (ILCs). Both ILC and T cells participated in interferon-γ (IFN-γ), IL-17, and IL-22 upregulation but in a time- and organ-specific manner. T cells were, however, necessary for colitis as mice depleted of Thy-1(+) cells were protected while neither Rag1(-/-) nor IL-10R blocked Rag1(-/-) mice developed colitis after infection. Depleting IFN-γ, IL-17, or both significantly ameliorated colitis and drove colonic responses toward type 2 cytokine and antibody induction. In contrast, C. jejuni GBS patient strains induced mild colitis associated with blunted type 1/17 but enhanced type 2 responses. Moreover, the type 2 but not type 1/17 antibodies cross-reacted with peripheral nerve gangliosides demonstrating autoimmunity.
1] Comparative Enteric Diseases Laboratory, Michigan State University, East Lansing, Michigan, USA [2] Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA.
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Malik
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA.
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Sharma
1] Comparative Enteric Diseases Laboratory, Michigan State University, East Lansing, Michigan, USA [2] Comparative Medicine and Integrative Biology Program, Michigan State University, East Lansing, Michigan, USA.
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St Charles
Comparative Enteric Diseases Laboratory, Michigan State University, East Lansing, Michigan, USA.
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Dybas
1] Comparative Enteric Diseases Laboratory, Michigan State University, East Lansing, Michigan, USA [2] Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA.
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Mansfield
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics; D002169:Campylobacter Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D016123:Campylobacter jejuni / Q000276:immunology*; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007111:Immunity, Cellular; D007113:Immunity, Innate; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D000907:Antibodies, Bacterial; D016207:Cytokines; D007074:Immunoglobulin G; D016753:Interleukin-10