Journal article
Targeting CBLB as a potential therapeutic approach for disseminated candidiasis
Nature medicine, Vol.22(8), pp.906-914
08/2016
DOI: 10.1038/nm.4141
PMCID: PMC4975523
PMID: 27428899
Abstract
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.
Details
- Title: Subtitle
- Targeting CBLB as a potential therapeutic approach for disseminated candidiasis
- Creators
- Yun Xiao - Department of Nephrology, Guangzhou Medical University, Guangzhou, P.R. ChinaJuan Tang - Department of Nephrology, Xiangya Hospital, Central South University, Changsha, P.R. ChinaHui Guo - Department of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USAYixia Zhao - Department of Cardiology, Xiangya Hospital, Central South University, Changsha, P.R. ChinaRong Tang - Department of Nephrology, Xiangya Hospital, Central South University, Changsha, P.R. ChinaSong Ouyang - Department of Neurology, First Hospital of Changsha, University of South China, Changsha, P.R. ChinaQiuming Zeng - Department of Neurology, Xiangya Hospital, Central South University, Changsha, P.R. ChinaChad A Rappleye - Department of Microbiology, Ohio State University, Columbus, Ohio, USAMurugesan V S Rajaram - Department of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USALarry S Schlesinger - Department of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USALijian Tao - Department of Nephrology, Xiangya Hospital, Central South University, Changsha, P.R. ChinaGordon D Brown - Aberdeen Fungal Group, MRC Centre for Medical Mycology, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UKWallace Y Langdon - School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, AustraliaBelinda T Li - Department of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USAJian Zhang - Department of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USA
- Resource Type
- Journal article
- Publication Details
- Nature medicine, Vol.22(8), pp.906-914
- DOI
- 10.1038/nm.4141
- PMID
- 27428899
- PMCID
- PMC4975523
- NLM abbreviation
- Nat Med
- ISSN
- 1078-8956
- eISSN
- 1546-170X
- Publisher
- Springer Science and Business Media LLC; United States
- Grant note
- 097377 / Wellcome Trust 102705 / Wellcome Trust R01 AI123253 / NIAID NIH HHS R01 AI090901 / NIAID NIH HHS R21 AI117547 / NIAID NIH HHS MR/N006364/1 / Medical Research Council
- Language
- English
- Date published
- 08/2016
- Academic Unit
- Pathology
- Record Identifier
- 9984046917102771
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