CARD9+ Microglia Orchestrate Antifungal Immunity via IL-1β and CXCL1-mediated Neutrophil Recruitment

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CARD9+ Microglia Orchestrate Antifungal Immunity via IL-1β and CXCL1-mediated Neutrophil Recruitment. / Drummond, Rebecca A.; Swamydas, Muthulekha; Oikonomou, Vasileios; Zhai, Bing; Dambuza, Ivy M.; Schaefer, Brian C.; Bohrer, Andrea C.; Mayer-barber, Katrin D.; Lira, Sergio A.; Iwakura, Yoichiro; Filler, Scott G.; Brown, Gordon D.; Hube, Bernhard; Naglik, Julian R.; Hohl, Tobias M.; Lionakis, Michail S.

In: Nature Immunology, Vol. 20, No. 5, 05.2019, p. 559–570.

Research output: Contribution to journalArticlepeer-review

Harvard

Drummond, RA, Swamydas, M, Oikonomou, V, Zhai, B, Dambuza, IM, Schaefer, BC, Bohrer, AC, Mayer-barber, KD, Lira, SA, Iwakura, Y, Filler, SG, Brown, GD, Hube, B, Naglik, JR, Hohl, TM & Lionakis, MS 2019, 'CARD9+ Microglia Orchestrate Antifungal Immunity via IL-1β and CXCL1-mediated Neutrophil Recruitment', Nature Immunology, vol. 20, no. 5, pp. 559–570. https://doi.org/10.1038/s41590-019-0377-2

APA

Drummond, R. A., Swamydas, M., Oikonomou, V., Zhai, B., Dambuza, I. M., Schaefer, B. C., Bohrer, A. C., Mayer-barber, K. D., Lira, S. A., Iwakura, Y., Filler, S. G., Brown, G. D., Hube, B., Naglik, J. R., Hohl, T. M., & Lionakis, M. S. (2019). CARD9+ Microglia Orchestrate Antifungal Immunity via IL-1β and CXCL1-mediated Neutrophil Recruitment. Nature Immunology, 20(5), 559–570. https://doi.org/10.1038/s41590-019-0377-2

Vancouver

Author

Drummond, Rebecca A. ; Swamydas, Muthulekha ; Oikonomou, Vasileios ; Zhai, Bing ; Dambuza, Ivy M. ; Schaefer, Brian C. ; Bohrer, Andrea C. ; Mayer-barber, Katrin D. ; Lira, Sergio A. ; Iwakura, Yoichiro ; Filler, Scott G. ; Brown, Gordon D. ; Hube, Bernhard ; Naglik, Julian R. ; Hohl, Tobias M. ; Lionakis, Michail S. / CARD9+ Microglia Orchestrate Antifungal Immunity via IL-1β and CXCL1-mediated Neutrophil Recruitment. In: Nature Immunology. 2019 ; Vol. 20, No. 5. pp. 559–570.

Bibtex

@article{c10130db92fe407882c9a44417e03664,
title = "CARD9+ Microglia Orchestrate Antifungal Immunity via IL-1β and CXCL1-mediated Neutrophil Recruitment",
abstract = "The C-type lectin receptor/Syk adaptor CARD9 facilitates protective antifungal immunity within the central nervous system (CNS), as human CARD9-deficiency causes fungal-specific CNS-targeted infection susceptibility. CARD9 is required for neutrophil recruitment to the fungal-infected CNS, which mediates fungal clearance. Here, we investigated host and pathogen factors that promote protective neutrophil recruitment during Candida albicans CNS invasion. IL-1β was essential for CNS antifungal immunity by driving CXCL1 production, which recruited CXCR2-expressing neutrophils. Neutrophil-recruiting IL-1β and CXCL1 production was induced in microglia by the fungal-secreted toxin Candidalysin, in a p38-cFos-dependent manner. Importantly, microglia relied on CARD9 for production of IL-1β, via both Il1b transcriptional regulation and inflammasome activation, and of CXCL1 in the fungal-infected CNS. Microglia-specific Card9 deletion impaired IL-1β and CXCL1 production and neutrophil recruitment, and increased CNS fungal proliferation. Taken together, an intricate network of host-pathogen interactions promotes CNS antifungal immunity, which is impaired in human CARD9-deficiency leading to CNS fungal disease. ",
author = "Drummond, {Rebecca A.} and Muthulekha Swamydas and Vasileios Oikonomou and Bing Zhai and Dambuza, {Ivy M.} and Schaefer, {Brian C.} and Bohrer, {Andrea C.} and Mayer-barber, {Katrin D.} and Lira, {Sergio A.} and Yoichiro Iwakura and Filler, {Scott G.} and Brown, {Gordon D.} and Bernhard Hube and Naglik, {Julian R.} and Hohl, {Tobias M.} and Lionakis, {Michail S.}",
year = "2019",
month = may,
doi = "10.1038/s41590-019-0377-2",
language = "English",
volume = "20",
pages = "559–570",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "5",

}

RIS

TY - JOUR

T1 - CARD9+ Microglia Orchestrate Antifungal Immunity via IL-1β and CXCL1-mediated Neutrophil Recruitment

AU - Drummond, Rebecca A.

AU - Swamydas, Muthulekha

AU - Oikonomou, Vasileios

AU - Zhai, Bing

AU - Dambuza, Ivy M.

AU - Schaefer, Brian C.

AU - Bohrer, Andrea C.

AU - Mayer-barber, Katrin D.

AU - Lira, Sergio A.

AU - Iwakura, Yoichiro

AU - Filler, Scott G.

AU - Brown, Gordon D.

AU - Hube, Bernhard

AU - Naglik, Julian R.

AU - Hohl, Tobias M.

AU - Lionakis, Michail S.

PY - 2019/5

Y1 - 2019/5

N2 - The C-type lectin receptor/Syk adaptor CARD9 facilitates protective antifungal immunity within the central nervous system (CNS), as human CARD9-deficiency causes fungal-specific CNS-targeted infection susceptibility. CARD9 is required for neutrophil recruitment to the fungal-infected CNS, which mediates fungal clearance. Here, we investigated host and pathogen factors that promote protective neutrophil recruitment during Candida albicans CNS invasion. IL-1β was essential for CNS antifungal immunity by driving CXCL1 production, which recruited CXCR2-expressing neutrophils. Neutrophil-recruiting IL-1β and CXCL1 production was induced in microglia by the fungal-secreted toxin Candidalysin, in a p38-cFos-dependent manner. Importantly, microglia relied on CARD9 for production of IL-1β, via both Il1b transcriptional regulation and inflammasome activation, and of CXCL1 in the fungal-infected CNS. Microglia-specific Card9 deletion impaired IL-1β and CXCL1 production and neutrophil recruitment, and increased CNS fungal proliferation. Taken together, an intricate network of host-pathogen interactions promotes CNS antifungal immunity, which is impaired in human CARD9-deficiency leading to CNS fungal disease.

AB - The C-type lectin receptor/Syk adaptor CARD9 facilitates protective antifungal immunity within the central nervous system (CNS), as human CARD9-deficiency causes fungal-specific CNS-targeted infection susceptibility. CARD9 is required for neutrophil recruitment to the fungal-infected CNS, which mediates fungal clearance. Here, we investigated host and pathogen factors that promote protective neutrophil recruitment during Candida albicans CNS invasion. IL-1β was essential for CNS antifungal immunity by driving CXCL1 production, which recruited CXCR2-expressing neutrophils. Neutrophil-recruiting IL-1β and CXCL1 production was induced in microglia by the fungal-secreted toxin Candidalysin, in a p38-cFos-dependent manner. Importantly, microglia relied on CARD9 for production of IL-1β, via both Il1b transcriptional regulation and inflammasome activation, and of CXCL1 in the fungal-infected CNS. Microglia-specific Card9 deletion impaired IL-1β and CXCL1 production and neutrophil recruitment, and increased CNS fungal proliferation. Taken together, an intricate network of host-pathogen interactions promotes CNS antifungal immunity, which is impaired in human CARD9-deficiency leading to CNS fungal disease.

U2 - 10.1038/s41590-019-0377-2

DO - 10.1038/s41590-019-0377-2

M3 - Article

VL - 20

SP - 559

EP - 570

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 5

ER -