1. Functional plasticity shapes neutrophil response to Leishmania major infection in susceptible and resistant strains of mice.
- Author
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DeSouza-Vieira T, Pretti MAM, Lima Gomes PS, Paula-Neto HA, Goundry A, Nascimento MT, Ganesan S, Gonçalves da Silva T, Kamenyeva O, Kabat J, Manzella-Lapeira J, B Canto F, Fraga-Junior VDS, Eustáquio Lopes M, Gomes Vaz L, Pessenda G, Paun A, Freitas-Mesquita AL, Meyer-Fernandes JR, Boroni M, Bellio M, Batista Menezes G, Brzostowski J, Mottram J, Sacks D, Lima APCA, and Saraiva EM
- Subjects
- Animals, Mice, Extracellular Traps immunology, Disease Susceptibility, Female, Leishmania major immunology, Neutrophils immunology, Leishmaniasis, Cutaneous immunology, Leishmaniasis, Cutaneous parasitology, Mice, Inbred BALB C, Mice, Inbred C57BL, Phagocytosis
- 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., 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.)
- Published
- 2024
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