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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
CARD9 + microglia promote antifungal immunity via IL-1β- and CXCL1-mediated neutrophil recruitment
Nature Immunology, Volume 20, No. 5, Year 2019
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Description
The C-type lectin receptor–Syk (spleen tyrosine kinase) adaptor CARD9 facilitates protective antifungal immunity within the central nervous system (CNS), as human deficiency in CARD9 causes susceptibility to fungus-specific, CNS-targeted infection. CARD9 promotes the recruitment of neutrophils to the fungus-infected CNS, which mediates fungal clearance. In the present study we investigated host and pathogen factors that promote protective neutrophil recruitment during invasion of the CNS by Candida albicans. The cytokine IL-1β served an essential function in CNS antifungal immunity by driving production of the chemokine CXCL1, which recruited neutrophils expressing the chemokine receptor CXCR2. Neutrophil-recruiting production of IL-1β and CXCL1 was induced in microglia by the fungus-secreted toxin Candidalysin, in a manner dependent on the kinase p38 and the transcription factor c-Fos. Notably, microglia relied on CARD9 for production of IL-1β, via both transcriptional regulation of Il1b and inflammasome activation, and of CXCL1 in the fungus-infected CNS. Microglia-specific Card9 deletion impaired the production of IL-1β and CXCL1 and neutrophil recruitment, and increased fungal proliferation in the CNS. Thus, an intricate network of host–pathogen interactions promotes antifungal immunity in the CNS; this is impaired in human deficiency in CARD9, which leads to fungal disease of the CNS. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
Authors & Co-Authors
Drummond, Rebecca A.
United States, Bethesda
National Institutes of Health Nih
United Kingdom, Birmingham
University of Birmingham
Swamydas, Muthulekha
United States, Bethesda
National Institutes of Health Nih
Dambuza, Ivy M.
United Kingdom, London
Medical Research Council
Schaefer, Brian C.
United States, Bethesda
Uniformed Services University of the Health Sciences
Bohrer, Andrea C.
United States, Bethesda
National Institutes of Health Nih
Mayer-Barber, Katrin D.
United States, Bethesda
National Institutes of Health Nih
Iwakura, Yoichiro
Japan, Tokyo
Tokyo University of Science
Filler, Scott G.
United States, Torrance
The Lundquist Institute
Brown, Gordon D.A.
United Kingdom, London
Medical Research Council
Lionakis, Michail
United States, Bethesda
National Institutes of Health Nih
Statistics
Citations: 138
Authors: 10
Affiliations: 11
Identifiers
Doi:
10.1038/s41590-019-0377-2
ISSN:
15292908