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

Autor:	Jaeger M; Department of Medicine, University of Colorado Denver, Aurora, USA.; Department of Internal Medicine, Radboud University Medical Center and Radboud Center for Infectious diseases (RCI), Nijmegen, the Netherlands., Dietschmann A; Junior Research Group Adaptive Pathogenicity Strategies, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany., Austermeier S; Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany., Dinçer S; Junior Research Group Adaptive Pathogenicity Strategies, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany., Porschitz P; Junior Research Group Adaptive Pathogenicity Strategies, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany., Vornholz L; Institute of Clinical Chemistry and Pathobiochemistry, School of Medicine and Health, Center for Translational Cancer Research (TranslaTUM), Munich, Germany., Maas RJA; Department of Medicine, University of Colorado Denver, Aurora, USA.; Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands., Sprenkeler EGG; Department of Internal Medicine, Radboud University Medical Center and Radboud Center for Infectious diseases (RCI), Nijmegen, the Netherlands., Ruland J; Institute of Clinical Chemistry and Pathobiochemistry, School of Medicine and Health, Center for Translational Cancer Research (TranslaTUM), Munich, Germany.; German Cancer Consortium (DKTK), partner site Munich, Germany.; German Center for Infection Research (DZIF), partner site Munich, Germany., Wirtz S; Medizinische Klinik 1, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Azam T; Department of Medicine, University of Colorado Denver, Aurora, USA., Joosten LAB; Department of Internal Medicine, Radboud University Medical Center and Radboud Center for Infectious diseases (RCI), Nijmegen, the Netherlands., Hube B; Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.; Institute of Microbiology, Friedrich-Schiller-University, Jena, Germany., Netea MG; Department of Internal Medicine, Radboud University Medical Center and Radboud Center for Infectious diseases (RCI), Nijmegen, the Netherlands., Dinarello CA; Department of Medicine, University of Colorado Denver, Aurora, USA.; Department of Internal Medicine, Radboud University Medical Center and Radboud Center for Infectious diseases (RCI), Nijmegen, the Netherlands., Gresnigt MS; Department of Medicine, University of Colorado Denver, Aurora, USA.; Junior Research Group Adaptive Pathogenicity Strategies, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.
Jazyk:	angličtina
Zdroj:	Virulence [Virulence] 2024 Dec; Vol. 15 (1), pp. 2333367. Date of Electronic Publication: 2024 Apr 10.
DOI:	10.1080/21505594.2024.2333367
Abstrakt:	Our 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:	MEDLINE
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