Syk Signaling in Dendritic Cells Orchestrates Innate Resistance to Systemic Fungal Infection

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Multiple cell types bearing a vast array of immune receptors with different modes of signaling ensure that the host response to infection is both robust and reliable. For this reason, loss of a single signaling pathway in a given cell type is often not enough to impact host resistance. Here, we find, surprisingly, that this is not the case in a mouse model of systemic fungal infection with Candida albicans. We show that a single kinase (Syk) in a single cell type (dendritic cells, DCs) coordinates the entire host resistance network. We highlight Syk-dependent production of IL-23p19 by DCs as the key to protection and show that IL-23p19 acts on another white blood cell type, NK cells, to specifically induce production of another mediator, GM-CSF. The latter is key for yet another cell, the neutrophil, to be mobilized into action and kill Candida organisms. This study places DCs, best known for their role in priming T cells, at the center of a cellular relay of innate immunity to fungal infection. It highlights key nodes of antifungal immunity that could be targeted in combination with antifungal drugs to provide new ways to treat patients with fungal sepsis, who generally have poor outcomes.

Vyšlo v časopise: Syk Signaling in Dendritic Cells Orchestrates Innate Resistance to Systemic Fungal Infection. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004276
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004276

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Zdroje

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