Functional plasticity shapes neutrophil response to Leishmania major infection in susceptible and resistant strains of mice.

Autor: DeSouza-Vieira T; Laboratório de Imunobiologia das Leishmanioses, Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Pretti MAM; Laboratório de Bioinformática e Biologia Computacional, Divisão de Pesquisa Experimental Translacional, Instituto Nacional do Câncer (INCA), Rio de Janeiro, Brasil., Lima Gomes PS; Laboratório de Imunobiologia das Leishmanioses, Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Paula-Neto HA; Laboratório de Alvos Moleculares, Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Goundry A; Laboratório de Bioquímica e Biologia Molecular de Proteases, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Nascimento MT; Laboratório de Imunobiologia das Leishmanioses, Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Ganesan S; Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America., Gonçalves da Silva T; National Center for Structural Biology and Bioimaging, CENABIO, Universidade Federal do Rio de Janeiro, Brazil., Kamenyeva O; Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America., Kabat J; Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America., Manzella-Lapeira J; Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America., B Canto F; Laboratório de Tolerância Imunológica e Homeostase Linfocitária, Departamento de Imunobiologia, Universidade Federal Fluminense, Rio de Janeiro, Rio de Janeiro, Brasil., Fraga-Junior VDS; Laboratório de Imunologia Molecular e Celular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Eustáquio Lopes M; Centro de Biologia Gastrointestinal, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil., Gomes Vaz L; Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Pampulha, Belo Horizonte, Minas Gerais, Brasil., Pessenda G; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America., Paun A; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America., Freitas-Mesquita AL; Instituto de Bioquímica Médica Leopoldo de Meis, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Meyer-Fernandes JR; Instituto de Bioquímica Médica Leopoldo de Meis, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Boroni M; Laboratório de Bioinformática e Biologia Computacional, Divisão de Pesquisa Experimental Translacional, Instituto Nacional do Câncer (INCA), Rio de Janeiro, Brasil., Bellio M; Laboratório de Imunobiologia, Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Batista Menezes G; Centro de Biologia Gastrointestinal, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil., Brzostowski J; Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America., Mottram J; York Biomedical Research Institute and Department of Biology, University of York, York, United Kingdom., Sacks D; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America., Lima APCA; Laboratório de Bioquímica e Biologia Molecular de Proteases, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil., Saraiva EM; Laboratório de Imunobiologia das Leishmanioses, Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Oct 08; Vol. 20 (10), pp. e1012592. Date of Electronic Publication: 2024 Oct 08 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012592
Abstrakt: Neutrophils rapidly infiltrate sites of infection and possess several microbicidal strategies, such as neutrophil extracellular traps release and phagocytosis. Enhanced neutrophil infiltration is associated with higher susceptibility to Leishmania infection, but neutrophil effector response contribution to this phenotype is uncertain. Here, we show that neutrophils from susceptible BALB/c mice (B/c) produce more NETs in response to Leishmania major than those from resistant C57BL/6 mice (B6), which are more phagocytic. The absence of neutrophil elastase contributes to phagocytosis regulation. Microarray analysis shows enrichment of genes involved in NET formation (mpo, pi3kcg, il1b) in B/c, while B6 shows upregulation of genes involved in phagocytosis and cell death (Arhgap12, casp9, mlkl, FasL). scRNA-seq in L. major-infected B6 showed heterogeneity in the pool of intralesional neutrophils, and we identified the N1 subset as the putative subpopulation involved with phagocytosis. In vivo, imaging validates NET formation in infected B/c ears where NETing neutrophils were mainly uninfected cells. NET digestion in vivo augmented parasite lymphatic drainage. Hence, a balance between NET formation and phagocytosis in neutrophils may contribute to the divergent phenotype observed in these mice.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)
Databáze: MEDLINE
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