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 (IFN?) 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.

Keywords (eng)

Signal TransductionAnimalsCandida Albicans ImmunologyTYK2 Kinase MetabolismTYK2 Kinase GeneticsMiceInterferon-gamma MetabolismInterferon-gamma ImmunologyNeutrophils ImmunologyNeutrophils MetabolismMice KnockoutMice Inbred C57BLSkin MicrobiologySkin ImmunologyCandidiasis ImmunologyCandidiasis MicrobiologyCandidiasis GeneticsFemaleWound Healing ImmunologyWound Healing GeneticsCandidiasis Cutaneous ImmunologyCandidiasis Cutaneous GeneticsCandidiasis, Cutaneous MetabolismCandidiasis Cutaneous MicrobiologyMale

Type (eng)

journal article

Language

[eng]

Persistent identifier

https://phaidra.vetmeduni.ac.at/o:3831

DOI

10.1038/s41467-024-54888-6

Is in series

Title (eng)

Nature Communications

Volume