Role of mincle in alveolar macrophage-dependent innate immunity against mycobacterial infections in mice

Friederike Behler, Kathrin Steinwede, Luciana Balboa, Bianca Ueberberg, Regina Maus, Gabriele Kirchhof, Sho Yamasaki, Tobias Welte, Ulrich A. Maus

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    52 Citations (Scopus)

    Abstract

    The role of macrophage-inducible C-type lectin Mincle in lung innate immunity against mycobacterial infection is incompletely defined. In this study, we show that wild-type (WT) mice responded with a delayed Mincle induction on resident alveolar macrophages and newly immigrating exudate macrophages to infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG), peaking by days 14-21 posttreatment. As compared with WT mice, Mincle knockout (KO) mice exhibited decreased proinflammatory mediator responses and leukocyte recruitment upon M. bovis BCG challenge, and they demonstrated increased mycobacterial loads in pulmonary and extrapulmonary organ systems. Secondary mycobacterial infection on day 14 after primary BCG challenge led to increased cytokine gene expression in sorted alveolar macrophages of WT mice, but not Mincle KO mice, resulting in substantially reduced alveolar neutrophil recruitment and increased mycobacterial loads in the lungs of Mincle KO mice. Collectively, these data show that WT mice respond with a relatively late Mincle expression on lung sentinel cells to M. bovis BCG infection. Moreover, M. bovis BCG-induced upregulation of C-type lectin Mincle on professional phagocytes critically shapes antimycobacterial responses in both pulmonary and extrapulmonary organ systems of mice, which may be important for elucidating the role of Mincle in the control of mycobacterial dissemination in mice.

    Original languageEnglish
    Pages (from-to)3121-3129
    Number of pages9
    JournalJournal of Immunology
    Volume189
    Issue number6
    DOIs
    Publication statusPublished - Sep 15 2012

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

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  • Cite this

    Behler, F., Steinwede, K., Balboa, L., Ueberberg, B., Maus, R., Kirchhof, G., Yamasaki, S., Welte, T., & Maus, U. A. (2012). Role of mincle in alveolar macrophage-dependent innate immunity against mycobacterial infections in mice. Journal of Immunology, 189(6), 3121-3129. https://doi.org/10.4049/jimmunol.1201399