Dysregulation of interleukin-10 and interleukin-12 are involved in the reduced host resistance toListeria monocytogenesinfection in alymphoplasticalymutant mice
Open Access
- 1 January 2002
- journal article
- Published by Oxford University Press (OUP) in FEMS Immunology & Medical Microbiology
- Vol. 32 (2) , 111-117
- https://doi.org/10.1111/j.1574-695x.2002.tb00542.x
Abstract
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-γ (IFN-γ) production are attenuated in the mutant mice. In this study, we investigated the mechanism of decrease in antilisterial resistance and IFN-γ 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-γ production was markedly decreased when macrophages derived from aly/aly mice were used. IFN-γ 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-γ 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-γ 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-γ-independent mechanism may be also involved in the decrease in antilisterial resistance in aly/aly mice.Keywords
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