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Lack of TYK2 Signaling Enhances Host Resistance to Candida albicans Skin Infection

ABSTRACT: Candida albicans is the most common human fungal pathogen, causing diseases ranging from local to life-threating systemic infections. Tyrosine kinase 2 (TYK2), a crucial mediator in several cytokine signaling pathways, has been associated with protective functions in various microbial infections. However, its specific contribution in the immune response to fungal infections has remained elusive. In this study, we show that mice lacking TYK2 or its enzymatic activity exhibit enhanced resistance to C. albicans skin infections, limiting fungal spread and accelerating wound healing. Impaired TYK2-signaling prompted the formation of a distinctive layer of necrotic neutrophils around the fungal pathogens. Transcriptomic analysis revealed TYK2's pivotal role in regulating interferon-inducible genes in neutrophils, thereby impacting their antifungal capacity during infection. Furthermore, we show that TYK2-dependent interferon-gamma (IFNg) production contributes to fungal dissemination from the skin to the kidneys. Our study uncovers a hitherto unrecognized detrimental role of TYK2 in cutaneous C. albicans infections.

ORGANISM(S): Mus musculus

PROVIDER: GSE278915 | GEO | 2024/10/14

REPOSITORIES: GEO

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Lack of TYK2 Signaling Enhances Host Resistance to Candida albicans Skin Infection

Project description:Lack of TYK2 Signaling Enhances Host Resistance to Candida albicans Skin Infection

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Comparison of the expression profiles of wild-type (WT), Tyk2-deficient (Tyk2-/-) and kinase-inactive Tyk2 mutant (Tyk2K923E) NK cells

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Project description:Peritoneal macrophages of Tyk2-/- and wildtype (wt) mice were compared before and after six hours of LPS treatment. Interferon responsive genes are lower expressed in Tyk2-/- macrophages at the basal level, metabolic genes higher before, but even more after LPS treatment. cDNA from macrophages from three replicates of three Tyk2-/- and three wt mice before and after six hours of LPS treatment, respectively, was hybridized to a microarray and analyzed.

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