Dendritic cells from C57BL/6 mice undergo activation and induce Th1-effector cell responses against Campylobacter jejuni.
Food-borne Campylobacter jejuni (Cj) is an important cause of enteritis. We showed that C57BL/6 and congenic interleukin (IL)-10(-/-) mice serve as models of Cj colonization and enteritis, respectively. Thus, C57BL/6 mice are resistant to Cj induced disease. Because dendritic cells (DCs) are central to regulating adaptive immune responses, we investigated the interaction of Cj with murine bone marrow-derived DCs (BM-DCs) to assess bacterial killing, DC activation, and the ability of Cj-infected BM-DCs to stimulate Campylobacter-specific T cell responses in vitro. BM-DCs challenged with Cj efficiently internalized and killed Cj 11168 and significantly upregulated surface MHC-II, CD40, CD80 and CD86 demonstrating a mature phenotype. Infected BM-DCs secreted significant amounts of tumor necrosis factor-alpha (TNF-alpha), IL-6 and IL-12p70. Formalin-killed Cj also induced maturation of BM-DCs with similar cytokine production but at a significantly lower magnitude than live bacteria. Maximal activation of murine BM-DCs required internalization of Cj; attachment alone was not sufficient to elicit significant responses. Also, various strains of Cj elicited different magnitudes of cytokine production from BM-DCs. Finally, in a coculture system, Cj-infected BM-DCs induced high level interferon-gamma (INF-gamma) production from CD4+T cells indicating Th1 polarization. Thus, DCs from resistant C57BL/6 mice initiate T cell responses against Cj.
Rathinam
Vijay A K
VA
Comparative Enteric Diseases Laboratory, Michigan State University, East Lansing, MI 48824, USA.
Hoag
Kathleen A
KA
Mansfield
Linda S
LS
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016123:Campylobacter jejuni / Q000276:immunology* / Q000472:pathogenicity; D002454:Cell Differentiation; D016764:Cell Polarity; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology*
D016207:Cytokines