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

Cryptococcus neoformans and Cryptococcus gattii cause life-threatening meningoencephalitis or lung diseases in immunocompetent individuals or immunocompromised ones. C. neoformans and C. gattii are subdivided into five serotypes based on their capsular glucuronoxylomannan (GXM). C. neoformans consis...

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Autores principales: Huang, Hua-Rong, Li, Fan, Han, Hua, Xu, Xia, Li, Ning, Wang, Shunchun, Xu, Jin-Fu, Jia, Xin-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090260/
https://www.ncbi.nlm.nih.gov/pubmed/30131805
http://dx.doi.org/10.3389/fimmu.2018.01781
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author Huang, Hua-Rong
Li, Fan
Han, Hua
Xu, Xia
Li, Ning
Wang, Shunchun
Xu, Jin-Fu
Jia, Xin-Ming
author_facet Huang, Hua-Rong
Li, Fan
Han, Hua
Xu, Xia
Li, Ning
Wang, Shunchun
Xu, Jin-Fu
Jia, Xin-Ming
author_sort Huang, Hua-Rong
collection PubMed
description Cryptococcus neoformans and Cryptococcus gattii cause life-threatening meningoencephalitis or lung diseases in immunocompetent individuals or immunocompromised ones. C. neoformans and C. gattii are subdivided into five serotypes based on their capsular glucuronoxylomannan (GXM). C. neoformans consists of serotypes A, D, and AD hybrid, and C. gattii consists of serotypes B and C. Given structural differences of GXM between C. neoformans and C. gattii, 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 C. neoformans serotype AD (C.n-AD) and C. gattii serotype B (C.g-B). GXMs from C.n-AD and C.g-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 C.n-AD and C.g-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 C.n-AD and C.g-B to initiate host defense against cryptococcosis.
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spelling pubmed-60902602018-08-21 Dectin-3 Recognizes Glucuronoxylomannan of Cryptococcus neoformans Serotype AD and Cryptococcus gattii Serotype B to Initiate Host Defense Against Cryptococcosis Huang, Hua-Rong Li, Fan Han, Hua Xu, Xia Li, Ning Wang, Shunchun Xu, Jin-Fu Jia, Xin-Ming Front Immunol Immunology Cryptococcus neoformans and Cryptococcus gattii cause life-threatening meningoencephalitis or lung diseases in immunocompetent individuals or immunocompromised ones. C. neoformans and C. gattii are subdivided into five serotypes based on their capsular glucuronoxylomannan (GXM). C. neoformans consists of serotypes A, D, and AD hybrid, and C. gattii consists of serotypes B and C. Given structural differences of GXM between C. neoformans and C. gattii, 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 C. neoformans serotype AD (C.n-AD) and C. gattii serotype B (C.g-B). GXMs from C.n-AD and C.g-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 C.n-AD and C.g-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 C.n-AD and C.g-B to initiate host defense against cryptococcosis. Frontiers Media S.A. 2018-08-06 /pmc/articles/PMC6090260/ /pubmed/30131805 http://dx.doi.org/10.3389/fimmu.2018.01781 Text en Copyright © 2018 Huang, Li, Han, Xu, Li, Wang, Xu and Jia. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Huang, Hua-Rong
Li, Fan
Han, Hua
Xu, Xia
Li, Ning
Wang, Shunchun
Xu, Jin-Fu
Jia, Xin-Ming
Dectin-3 Recognizes Glucuronoxylomannan of Cryptococcus neoformans Serotype AD and Cryptococcus gattii Serotype B to Initiate Host Defense Against Cryptococcosis
title Dectin-3 Recognizes Glucuronoxylomannan of Cryptococcus neoformans Serotype AD and Cryptococcus gattii Serotype B to Initiate Host Defense Against Cryptococcosis
title_full Dectin-3 Recognizes Glucuronoxylomannan of Cryptococcus neoformans Serotype AD and Cryptococcus gattii Serotype B to Initiate Host Defense Against Cryptococcosis
title_fullStr Dectin-3 Recognizes Glucuronoxylomannan of Cryptococcus neoformans Serotype AD and Cryptococcus gattii Serotype B to Initiate Host Defense Against Cryptococcosis
title_full_unstemmed Dectin-3 Recognizes Glucuronoxylomannan of Cryptococcus neoformans Serotype AD and Cryptococcus gattii Serotype B to Initiate Host Defense Against Cryptococcosis
title_short Dectin-3 Recognizes Glucuronoxylomannan of Cryptococcus neoformans Serotype AD and Cryptococcus gattii Serotype B to Initiate Host Defense Against Cryptococcosis
title_sort dectin-3 recognizes glucuronoxylomannan of cryptococcus neoformans serotype ad and cryptococcus gattii serotype b to initiate host defense against cryptococcosis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090260/
https://www.ncbi.nlm.nih.gov/pubmed/30131805
http://dx.doi.org/10.3389/fimmu.2018.01781
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