AUTHOR=Huang Hua-Rong , Li Fan , Han Hua , Xu Xia , Li Ning , Wang Shunchun , Xu Jin-Fu , Jia Xin-Ming 

TITLE=Dectin-3 Recognizes Glucuronoxylomannan of Cryptococcus neoformans Serotype AD and Cryptococcus gattii Serotype B to Initiate Host Defense Against Cryptococcosis

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01781

DOI=10.3389/fimmu.2018.01781

ISSN=1664-3224

ABSTRACT=<p><italic>Cryptococcus neoformans</italic> and <italic>Cryptococcus gattii</italic> cause life-threatening meningoencephalitis or lung diseases in immunocompetent individuals or immunocompromised ones. <italic>C. neoformans</italic> and <italic>C. gattii</italic> are subdivided into five serotypes based on their capsular glucuronoxylomannan (GXM). <italic>C. neoformans</italic> consists of serotypes A, D, and AD hybrid, and <italic>C. gattii</italic> consists of serotypes B and C. Given structural differences of GXM between <italic>C. neoformans</italic> and <italic>C. gattii</italic>, it remains unclear that how innate immune system recognizes GXM. Here, we report that C-type lectin receptor Dectin-3 (MCL encoded by Clec4d) is a direct receptor for GXMs from <italic>C. neoformans</italic> serotype AD (<italic>C.n</italic>-AD) and <italic>C. gattii</italic> serotype B (<italic>C.g</italic>-B). GXMs from <italic>C.n</italic>-AD and <italic>C.g</italic>-B activated NF-κB and ERK pathways to induce pro-inflammatory cytokine production, whereas it was completely abolished due to deficiency of Dectin-3 or caspase recruitment domain family member 9 (CARD9). Upon pulmonary <italic>C.n</italic>-AD and <italic>C.g</italic>-B infection, Dectin-3- and CARD9-deficient mice were highly susceptible and showed augmented lung injury due to impairment of alveolar macrophage accumulation and killing activities. Our study provides the first biological and genetic evidence demonstrating that Dectin-3 recognizes GXM of <italic>C.n</italic>-AD and <italic>C.g</italic>-B to initiate host defense against cryptococcosis.</p>