IL-12 is essential for resistance against Yersinia enterocolitica by triggering IFN-gamma production in NK cells and CD4+ T cells.
Although Yersinia enterocolitica is extracellularly located in infected tissues, a specific T cell response is required to overcome infection. Recent work implicated that in contrast to Yersinia-susceptible BALB/c mice, C57BL/6 mice are Yersinia resistant due to the rapid development of a Yersinia-specific Th1 T cell response. This study focused on the role of IL-12 in Y. enterocolitica infections in both mouse strains. We found that C57BL/6 and BALB/c mice produced comparable quantities of IL-12 mRNA after Y. enterocolitica infection. Likewise, Yersinia-infected bone marrow macrophages from both mouse strains produced equal quantities of IL-12. Administration of neutralizing anti-IL-12 Abs abrogated resistance against yersiniae in either strain. In addition, administration of rIL-12 rendered BALB/c mice resistant to yersiniae, while this treatment was toxic to C57BL/6 mice. IL-12-mediated protection was partially dependent on IFN-gamma. Spleen cells from both strains of mice produced Yersinia-triggered IFN-gamma in an IL-12-dependent manner, although those from BALB/c mice produced 10-fold lesser quantities. Administration of rIL-12 in vivo increased Yersinia-induced IFN-gamma production by BALB/c spleen cells in vitro, but decreased IFN-gamma production by spleen cells from C57BL/6 mice. IL-10 was antagonistic to IL-12 only in BALB/c mice and inhibited Yersinia-triggered IFN-gamma production. In vivo depletion experiments revealed that IL-12 accounts for Yersinia-induced IFN-gamma production by both NK cells and CD4+ T cells, the latter of which are an essential source of IFN-gamma r while NK cell-derived IFN-gamma production can be compensated by other cells. In contrast to that in the spleen, IL-12 plays a minor role in protection against yersiniae in Peyer's patches after orogastric infection. In summary, our data suggest that IL-12 is rapidly induced by Y. enterocolitica infection and required for IFN-gamma production by NK cells as well by CD4+ T cells. Although BALB/c and C57BL/6 mice produced comparable quantities of IL-12, IFN-gamma production, and thus resistance to yersiniae, can be increased by exogenous IL-12 only in BALB/c, not in C57BL/6, mice.
Bohn
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Institute for Hygiene and Microbiology, Wurzburg University, Germany.
Autenrieth
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D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010581:Peyer's Patches / Q000276:immunology; D013154:Spleen / Q000276:immunology; D015009:Yersinia Infections / Q000276:immunology*; D015008:Yersinia enterocolitica / Q000276:immunology*
D017931:DNA Primers; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma