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

First Author  Oh S Year  2022
Journal  Cell Rep Volume  38
Issue  13 Pages  110567
PubMed ID  35354044 Mgi Jnum  J:358550
Mgi Id  MGI:7286509 Doi  10.1016/j.celrep.2022.110567
Citation  Oh S, et al. (2022) Pathogen size alters C-type lectin receptor signaling in dendritic cells to influence CD4 Th9 cell differentiation. Cell Rep 38(13):110567
abstractText  Dectin-1 recognizes beta-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 TH9 responses. Expression of IL-33 is regulated by the Dectin-1-SYK-PLCgamma-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.
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