CD8α+ and CD8α DC subsets from BCG-infected mice inhibit allergic Th2-cell responses by enhancing Th1-cell and Treg-cell activity respectively

Authors

  • Xiaoling Gao,

    1. Laboratory for Infection and Immunity, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
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  • Hong Bai,

    1. Laboratory for Infection and Immunity, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
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  • Jianjun Cheng,

    1. Laboratory for Infection and Immunity, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
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  • Yijun Fan,

    1. Laboratory for Infection and Immunity, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
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  • Shuhe Wang,

    1. Laboratory for Infection and Immunity, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
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  • Lei Jiao,

    1. Laboratory for Infection and Immunity, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
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  • Nan Xiu,

    1. Laboratory for Infection and Immunity, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
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  • Xi Yang

    Corresponding author
    1. Laboratory for Infection and Immunity, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
    • Department of Medical Microbiology, University of Manitoba, Room 523, 730 William Avenue, Winnipeg, Manitoba, R3E 0W3, Canada Fax: 1-204-789-3926

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Abstract

The hygiene hypothesis has suggested an inhibitory effect of infections on allergic diseases, but the related mechanism remains unclear. We recently reported that DCs played a critical role in Mycobacterium bovis Bacille Calmette–Guérin (BCG)-mediated inhibition of allergy, which depended on IL-12 and IL-10-related mechanisms. Here, we tested the hypothesis that BCG infection could modulate the function of DC subsets, which might in turn inhibit allergic responses through different mechanisms. We sorted CD8α+ and CD8α DCs from BCG-infected mice and tested their ability to modulate Th2-cell responses to ovalbumin (OVA) using in vitro and in vivo approaches. We found that both DC subsets could inhibit the allergic Th2-cell response in both a DC:T-cell co-culture system and after adoptive transfer. These subsets exhibited different co-stimulatory marker expression and cytokine production patterns and were different in inducing Th1 and Treg cells. Specifically, we found that CD8α+ DCs produced higher IL-12, inducing higher Th1 cell response, while CD8α DCs expressed higher ICOS-L and produced higher IL-10, inducing CD4+CD25+FoxP3+Treg cells with IL-10 production and membrane-bound TGF-β expression. The finding suggests that one infection may inhibit allergy by both immune deviation and regulation mechanisms through modulation of DC subsets.

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