Alpha1-antitrypsin impacts innate host–pathogen interactions with Candida albicans by stimulating fungal filamentation

Autor: Martin Jaeger, Axel Dietschmann, Sophie Austermeier, Sude Dinçer, Pauline Porschitz, Larsen Vornholz, Ralph J.A. Maas, Evelien G.G. Sprenkeler, Jürgen Ruland, Stefan Wirtz, Tania Azam, Leo A.B. Joosten, Bernhard Hube, Mihai G. Netea, Charles A. Dinarello, Mark S. Gresnigt
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Virulence, Vol 15, Iss 1 (2024)
Druh dokumentu: article
ISSN: 21505594
2150-5608
2150-5594
DOI: 10.1080/21505594.2024.2333367
Popis: ABSTRACTOur immune system possesses sophisticated mechanisms to cope with invading microorganisms, while pathogens evolve strategies to deal with threats imposed by host immunity. Human plasma protein α1-antitrypsin (AAT) exhibits pleiotropic immune-modulating properties by both preventing immunopathology and improving antimicrobial host defence. Genetic associations suggested a role for AAT in candidemia, the most frequent fungal blood stream infection in intensive care units, yet little is known about how AAT influences interactions between Candida albicans and the immune system. Here, we show that AAT differentially impacts fungal killing by innate phagocytes. We observed that AAT induces fungal transcriptional reprogramming, associated with cell wall remodelling and downregulation of filamentation repressors. At low concentrations, the cell-wall remodelling induced by AAT increased immunogenic β-glucan exposure and consequently improved fungal clearance by monocytes. Contrastingly, higher AAT concentrations led to excessive C. albicans filamentation and thus promoted fungal immune escape from monocytes and macrophages. This underscores that fungal adaptations to the host protein AAT can differentially define the outcome of encounters with innate immune cells, either contributing to improved immune recognition or fungal immune escape.
Databáze: Directory of Open Access Journals
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