Human airway epithelium controls Pseudomonas aeruginosa infection via inducible nitric oxide synthase.

Autor:	Grubwieser P; Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, Innsbruck, Austria.; Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria., Böck N; Biocenter, Institute of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria., Soto EK; Biocenter, Institute of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria., Hilbe R; Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, Innsbruck, Austria., Moser P; INNPATH, Innsbruck Medical University Hospital, Innsbruck, Austria., Seifert M; Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, Innsbruck, Austria., Dichtl S; Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria., Govrins MA; Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria., Posch W; Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria., Sonnweber T; Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, Innsbruck, Austria., Nairz M; Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, Innsbruck, Austria., Theurl I; Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, Innsbruck, Austria., Trajanoski Z; Biocenter, Institute of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria., Weiss G; Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, Innsbruck, Austria.; Christian Doppler Laboratory for Iron Metabolism and Anemia Research, Medical University of Innsbruck, Innsbruck, Austria.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Dec 03; Vol. 15, pp. 1508727. Date of Electronic Publication: 2024 Dec 03 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1508727
Abstrakt:	Introduction: Airway epithelial cells play a central role in the innate immune response to invading bacteria, yet adequate human infection models are lacking. Methods: We utilized mucociliary-differentiated human airway organoids with direct access to the apical side of epithelial cells to model the initial phase of Pseudomonas aeruginosa respiratory tract infection. Results: Immunofluorescence of infected organoids revealed that Pseudomonas aeruginosa invades the epithelial barrier and subsequently proliferates within the epithelial space. RNA sequencing analysis demonstrated that Pseudomonas infection stimulated innate antimicrobial immune responses, but specifically enhanced the expression of genes of the nitric oxide metabolic pathway. We demonstrated that activation of inducible nitric oxide synthase (iNOS) in airway organoids exposed bacteria to nitrosative stress, effectively inhibiting intra-epithelial pathogen proliferation. Pharmacological inhibition of iNOS resulted in expansion of bacterial proliferation whereas a NO producing drug reduced bacterial numbers. iNOS expression was mainly localized to ciliated epithelial cells of infected airway organoids, which was confirmed in primary human lung tissue during Pseudomonas pneumonia. Discussion: Our findings highlight the critical role of epithelial-derived iNOS in host defence against Pseudomonas aeruginosa infection. Furthermore, we describe a human tissue model that accurately mimics the airway epithelium, providing a valuable framework for systemically studying host-pathogen interactions in respiratory infections. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Grubwieser, Böck, Soto, Hilbe, Moser, Seifert, Dichtl, Govrins, Posch, Sonnweber, Nairz, Theurl, Trajanoski and Weiss.)
Databáze:	MEDLINE
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