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

ABSTRACT: 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 Dectin-1 activated DCs induce different subsets of T helper cells according to different cytokine milieus, the precise mechanisms underlying such differences remain unknown. By harnessing polymorphic Candida albicans and polystyrene beads of different sizes, we found that target size influences production of cytokine that control differentiation of T helper cell subsets. Hyphal C. albicans and large beads activate DCs but cannot be phagocytosed due to their size, which prolongs the duration of Dectin-1 signaling. Transcriptomic analysis revealed that the expression of Il33 was significantly increased by larger targets, and increased IL-33 expression promoted TH9 responses. Expression of IL-33 was regulated by Dectin-1-SYK-PLCγ-CARD9-ERK pathway. Altogether, our study demonstrates that size of fungi can be a determining factor in which DCs induce context-appropriate adaptive immune responses.

ORGANISM(S): Mus musculus

PROVIDER: GSE181734 | GEO | 2022/04/01

REPOSITORIES: GEO

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