Targeting CBLB as a potential therapeutic approach for disseminated candidiasis

Y. Xiao, J. Tang, H. Guo, Y. Zhao, R. Tang, S. Ouyang, Q. Zeng, C.A. Rappleye, M.V.S. Rajaram, L.S. Schlesinger, L. Tao, G.D. Brown, Wallace Y. Langdon, B.T. Li, J. Zhang

    Research output: Contribution to journalArticle

    39 Citations (Scopus)

    Abstract

    © 2016 Nature America, Inc. All rights reserved.Disseminated candidiasis has become one of the leading causes of hospital-acquired blood stream infections with high mobility and mortality. However, the molecular basis of host defense against disseminated candidiasis remains elusive, and treatment options are limited. Here we report that the E3 ubiquitin ligase CBLB directs polyubiquitination of dectin-1 and dectin-2, two key pattern-recognition receptors for sensing Candida albicans, and their downstream kinase SYK, thus inhibiting dectin-1- and dectin-2-mediated innate immune responses. CBLB deficiency or inactivation protects mice from systemic infection with a lethal dose of C. albicans, and deficiency of dectin-1, dectin-2, or both in Cblb-/- mice abrogates this protection. Notably, silencing the Cblb gene in vivo protects mice from lethal systemic C. albicans infection. Our data reveal that CBLB is crucial for homeostatic control of innate immune responses mediated by dectin-1 and dectin-2. Our data also indicate that CBLB represents a potential therapeutic target for protection from disseminated candidiasis.
    Original languageEnglish
    Pages (from-to)906-914
    Number of pages9
    JournalNature Medicine
    Volume22
    Issue number8
    DOIs
    Publication statusPublished - 2016

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