Pathogen size alters C-type lectin receptor signaling in dendritic cells to influence CD4 Th9 cell differentiation.

Autor: Oh S; F. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA; Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Graduate Program in Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA., Li K; F. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA; Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA., Prince A; F. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA; Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA., Wheeler ML; F. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA; Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA., Hamade H; F. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA; The Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA., Nguyen C; F. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA; Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA., Michelsen KS; F. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA; Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; The Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA., Underhill DM; F. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA; Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; The Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address: david.underhill@csmc.edu.
Jazyk: angličtina
Zdroj: Cell reports [Cell Rep] 2022 Mar 29; Vol. 38 (13), pp. 110567.
DOI: 10.1016/j.celrep.2022.110567
Abstrakt: Dectin-1 recognizes β-glucan in fungal cell walls, and activation of Dectin-1 in dendritic cells (DCs) influences immune responses against fungi. Although many studies have shown that DCs activated via Dectin-1 induce different subsets of T helper cells according to different cytokine milieus, the mechanisms underlying such differences remain unknown. By harnessing polymorphic Candida albicans and polystyrene beads of different sizes, we find that target size influences production of cytokines that control differentiation of T helper cell subsets. Hyphal C. albicans and large beads activate DCs but cannot be phagocytosed due to their sizes, which prolongs the duration of Dectin-1 signaling. Transcriptomic analysis reveals that expression of Il33 is significantly increased by larger targets, and increased IL-33 expression promotes T H 9 responses. Expression of IL-33 is regulated by the Dectin-1-SYK-PLCγ-CARD9-ERK pathway. Altogether, our study demonstrates that size of fungi can be a determining factor in how DCs induce context-appropriate adaptive immune responses.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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