Differential effects of viable and killed bacteria on IL-12 expression of macrophages.
Listeria monocytogenes-specific, IFN-gamma-producing CD4+ T cells are induced in 5-day in vitro cultures of naive spleen cells with viable L. monocytogenes (VLM) but are not induced in cultures with heat killed L. monocytogenes (HKLM). Anti-IL-12 Abs abrogated the induction of the IFN-gamma-producing CD4+ T cells by VLM, suggesting an importance of IL-12 in the induction of IFN-gamma-producing CD4+ T cells. Accordingly, IL-12p40 was expressed by macrophages (M phi) from the cultures of whole spleen cells with VLM but not with HKLM, although HKLM induced IL-12p40 expression on M phi when nonadherent cells were removed before culture. In vivo analysis also showed that VLM induced IL-12p40 expression by M phi, whereas HKLM failed to induce it. On the other hand, the addition of anti-IL-10 mAb into cultures of whole spleen cells and HKLM resulted in an increase of IL-12p40 expression by M phi. Furthermore, we detected an expression of IFN-gamma by both adherent and nonadherent spleen cells at the early stage of stimulation with VLM before the appearance of IFN-gamma-producing CD4+ T cells. These data suggest that HKLM induce nonadherent spleen cells to produce IL-10 which may down-regulate IFN-gamma-producing CD4+ T cells by blocking IL-12 production by M phi. In contrast, VLM support IFN-gamma production by CD4+ T cells by stimulating M phi to produce IL-12 and IFN-gamma.
Song
F
F
Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Matsuzaki
G
G
Mitsuyama
M
M
Nomoto
K
K
D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D001483:Base Sequence; D002478:Cells, Cultured; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000502:physiology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D008089:Listeria monocytogenes / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000378:metabolism; D014613:Vaccines, Attenuated / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000276:immunology*
D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma