Dysregulation of interleukin-10 and interleukin-12 are involved in the reduced host resistance to Listeria monocytogenes infection in alymphoplastic aly mutant mice.
The aly is a unique spontaneous autosomal recessive mutation in mice that causes a systemic defect of lymph nodes and Peyer's patches and disorganized splenic and thymic structures with immunodeficiency. Our previous study demonstrated that resistance to Listeria monocytogenes infection and interferon-gamma (IFN-gamma) production are attenuated in the mutant mice. In this study, we investigated the mechanism of decrease in antilisterial resistance and IFN-gamma production in aly mice. Interleukin (IL)-12 production in response to heat-killed L. monocytogenes (HK-LM) was decreased but IL-10 production was increased in aly/aly macrophage cultures, compared with those in aly/+ macrophages. Nonadherent cells and macrophages obtained from the spleens of naive aly/+ mice and aly/aly mice were reconstituted and stimulated with HK-LM. IFN-gamma production was markedly decreased when macrophages derived from aly/aly mice were used. IFN-gamma production in aly/aly spleen cell cultures was recovered in the presence of anti-IL-10 monoclonal antibody (mAb) or recombinant IL-12. When aly/+ mice and aly/aly mice were injected with mAb against IL-10 or IL-12 p40, antilisterial resistance was inhibited by injection of anti-IL-12 p40 mAb, while anti-IL-10 mAb treatment augmented the resistance. Administration of anti-IFN-gamma mAb attenuated antilisterial resistance in aly/+ mice but not in aly/aly mice. The present results suggest that downregulation of IL-12 and upregulation of IL-10 in macrophages might be involved in the decrease in antilisterial resistance and IFN-gamma production in aly/aly mice in addition to the structural defect in lymphoid organs. Moreover, the results predict that an IL-12-dependent and IFN-gamma-independent mechanism may be also involved in the decrease in antilisterial resistance in aly/aly mice.
Hasegawa
Suguru
S
Department of Bacteriology, Hirosaki University School of Medicine, Aomori, Japan.
Miura
Tomisato
T
Sasaki
Sanae
S
Madarame
Hiroo
H
Nakane
Akio
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology*; D020382:Interleukin-18 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma