Hiding in the yolk: A unique feature of Legionella pneumophila infection of zebrafish.

Autor: Viana F; Institut Pasteur, Université Paris Cité, Université Paris Cité, Biologie des Bactéries Intracellulaires and CNRS UMR 6047, Paris, France., Boucontet L; Institut Pasteur, Université Paris Cité, Unité Macrophages et Développement de l'Immunité and CNRS UMR 3738, Paris, France., Laghi V; Institut Pasteur, Université Paris Cité, Unité Macrophages et Développement de l'Immunité and CNRS UMR 3738, Paris, France., Schator D; Institut Pasteur, Université Paris Cité, Université Paris Cité, Biologie des Bactéries Intracellulaires and CNRS UMR 6047, Paris, France.; Sorbonne Université, Collège doctoral, Paris, France., Ibranosyan M; National Reference Centre of Legionella, Institute of Infectious Agents, Hospices Civils de Lyon, Lyon, France., Jarraud S; National Reference Centre of Legionella, Institute of Infectious Agents, Hospices Civils de Lyon, Lyon, France.; Centre International de Recherche en Infectiologie, Université Lyon 1, UMR CNRS 5308, Inserm U1111, ENS de Lyon, Lyon, France., Colucci-Guyon E; Institut Pasteur, Université Paris Cité, Unité Macrophages et Développement de l'Immunité and CNRS UMR 3738, Paris, France., Buchrieser C; Institut Pasteur, Université Paris Cité, Université Paris Cité, Biologie des Bactéries Intracellulaires and CNRS UMR 6047, Paris, France.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2023 May 08; Vol. 19 (5), pp. e1011375. Date of Electronic Publication: 2023 May 08 (Print Publication: 2023).
DOI: 10.1371/journal.ppat.1011375
Abstrakt: The zebrafish has become a powerful model organism to study host-pathogen interactions. Here, we developed a zebrafish model to dissect the innate immune response to Legionella pneumophila during infection. We show that L. pneumophila cause zebrafish larvae death in a dose dependent manner. Additionally, we show that macrophages are the first line of defence and cooperate with neutrophils to clear the infection. Immunocompromised humans have an increased propensity to develop pneumonia, similarly, when either macrophages or neutrophils are depleted, these "immunocompromised" larvae become lethally sensitive to L. pneumophila. Also, as observed in human infections, the adaptor signalling molecule Myd88 is not required to control disease in the larvae. Furthermore, proinflammatory cytokine genes il1β and tnf-α were upregulated during infection, recapitulating key immune responses seen in human infection. Strikingly, we uncovered a previously undescribed infection phenotype in zebrafish larvae, whereby bloodborne, wild type L. pneumophila invade and grow in the larval yolk region, a phenotype not observed with a type IV secretion system deficient mutant that cannot translocate effectors into its host cell. Thus, zebrafish larva represents an innovative L. pneumophila infection model that mimics important aspects of the human immune response to L. pneumophila infection and will allow the elucidation of mechanisms by which type IV secretion effectors allow L. pneumophila to cross host cell membranes and obtain nutrients from nutrient rich environments.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Viana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje