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

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.

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Publication Details

Journal
PLoS Pathogens
Published
2024-10-08
DOI
https://doi.org/10.1371/journal.ppat.1012592
Citations
5
Primary Topic
Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Type
article
Field-Weighted Citation Impact
1.20

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article

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

Mariana Boroni, Michelle T. C. Nascimento, David B. Sacks, Amy Goundry et al.
5 citations
PLoS Pathogens
Neutrophil, Myeloperoxidase and Oxidative Mechanisms
1.20
article

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

Mariana Boroni, Michelle T. C. Nascimento, David B. Sacks, Amy Goundry, Leonardo Gomes Vaz, Ana Paula C. A. Lima, Jeremy C. Mottram, Vanderlei da Silva Fraga‐Junior, Fábio B. Canto, Maria Bellio, Marco Antônio M. Pretti, Sundar Ganesan, Gabriela Pessenda, Mateus Eustáquio Lopes, Andrea Paun, Joseph Brzostowski, Javier Manzella‐Lapeira, Olena Kamenyeva, José Roberto Meyer‐Fernandes, Juraj Kabát, Gustavo Batista Menezes, Thiago DeSouza‐Vieira, Anita Leocádio Freitas-Mesquita, Elvira M. Saraiva, Phillipe Souza Lima Gomes, Heitor A. Paula-Neto, Triciana Gonçalves da Silva
article en
5 citations

Abstract

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.

PLoS PathogensVol. 20(10)
Universidade Federal de Minas Gerais (BR), Universidade Federal do Rio de Janeiro (BR), National Institutes of Health (US), Universidade Federal Fluminense (BR), National Institute of Allergy and Infectious Diseases (US), National Institute of Science and Technology for Structural Biology and Bioimaging (BR), Instituto Nacional de Câncer - INCA (BR), University of York (GB)
Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Newton Fund, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Institut National Du Cancer, Universidade Federal de Minas Gerais, Universidade Federal do Rio de Janeiro, National Institutes of Health, Medical Research Council, National Institute of Allergy and Infectious Diseases, NHLBI Division of Intramural Research
Openalex Percentile: Top 21%
Neutrophil, Myeloperoxidase and Oxidative Mechanisms
1.20
DOIOpen Access PDFOpenAlex
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