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 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 Type1 and 17 but not Type2 cytokines in the colon coincident with infiltration of phagocytes, T cells and Innate Lymphoid Cells (ILC's). Both ILC and T cells participated in 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 towards Type2 cytokine and antibody induction. In contrast, C. jejuni GBS patient strains induced mild colitis associated with blunted Type1/17 but enhanced Type2 responses. Moreover, the Type2 but not Type1/17 antibodies cross-reacted with peripheral nerve gangliosides demonstrating autoimmunity.