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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
The protective effect of inflammatory monocytes during systemic C. Albicans infection is dependent on collaboration between C-type lectin-like receptors
PLoS Pathogens, Volume 15, No. 6, Article e1007850, Year 2019
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Description
Invasive candidiasis, mainly caused by Candida albicans, is a serious healthcare problem with high mortality rates, particularly in immunocompromised patients. Innate immune cells express pathogen recognition receptors (PRRs) including C-type lectin-like receptors (CLRs) that bind C. albicans to initiate an immune response. Multiple CLRs including Dectin-1, Dectin-2 and Mincle have been proposed individually to contribute to the immune response to C. albicans. However how these receptors collaborate to clear a fungal infection is unknown. Herein, we used novel multi-CLR knockout (KO) mice to decipher the individual, collaborative and collective roles of Dectin-1, Dectin-2 and Mincle during systemic C. albicans infection. These studies revealed an unappreciated and profound role for CLR cooperation in anti-fungal immunity. The protective effect of multiple CLRs was markedly greater than any single receptor, and was mediated through inflammatory monocytes via recognition and phagocytosis of C. albicans, and production of C. albicans-induced cytokines and chemokines. These CLRs were dispensable for mediating similar responses from neutrophils, likely due to lower expression of these CLRs on neutrophils compared to inflammatory monocytes. Concurrent deletion of Dectin-1 and Dectin-2, or all three CLRs, resulted in dramatically increased susceptibility to systemic C. albicans infection compared to mice lacking a single CLR. Multi-CLR KO mice were unable to control fungal growth due to an inadequate early inflammatory monocyte-mediated response. In response to excessive fungal growth, the multi-CLR KO mice mounted a hyper-inflammatory response, likely leading to multiple organ failure. Thus, these data reveal a critical role for CLR co-operation in the effective control of C. albicans and maintenance of organ function during infection. © 2019 Thompson et al.
Authors & Co-Authors
Davies, Luke C.
United Kingdom, Cardiff
Cardiff University School of Medicine
Liao, Chiate
United Kingdom, Cardiff
Cardiff University School of Medicine
Andrews, Robert M.
United Kingdom, Cardiff
Cardiff University School of Medicine
Brown, Gordon D.A.
United Kingdom, London
Medical Research Council
Humphreys, Ian Robert
United Kingdom, Cardiff
Cardiff University School of Medicine
Taylor, Philip Russel
United Kingdom, Cardiff
Cardiff University School of Medicine
Statistics
Citations: 32
Authors: 6
Affiliations: 3
Identifiers
Doi:
10.1371/journal.ppat.1007850
ISSN:
15537366
Research Areas
Health System And Policy