Role of the lipoxin A4 receptor in the development of neutrophil extracellular traps in Leishmania infantum infection

Furong Wei,Jianping Cao,Junyun Wang,Yuetao Yang,Jianxiu Liu,Wenci Gong,Yanjuan Wang

doi:10.1186/s13071-019-3530-8

Furong Wei, Jianping Cao + Show 5 more

Open Access

https://doi.org/10.1186/s13071-019-3530-8

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Journal: Parasites & Vectors	Publication Date: May 29, 2019
Citations: 13	License type: open-access

Affiliation: National Institute for Parasitic Diseases

Abstract

BackgroundNeutrophils play an immunomodulatory role through the release of neutrophil extracellular traps (NETs). NETs are released in response to Leishmania infection, but the mechanism of NET extrusion has not been elucidated. The lipoxin A4 receptor on neutrophils is crucial for the inflammatory response and immune regulation of many diseases, including Leishmania infection. Therefore, in the present study, we tried to explore whether Leishmania infantum promastigotes stimulate neutrophil activation and NET release via activating the lipoxin A4 receptor.ResultsLeishmania infantum promastigotes stimulated neutrophil activity, but blocking of the lipoxin A4 receptor with its antagonist Boc prior to L. infantum stimulation abrogated these effects. Neutrophils showed citrullinated histone H3 expression and simultaneous NET extrusion on L. infantum stimulation, but a decline in both was observed on blocking of the lipoxin A4 receptor. Moreover, differentiated HL-60 cells with lipoxin A4 receptor silencing showed a decrease in citrullinated histone H3 expression as compared to the unsilenced HL-60 samples on stimulation with promastigotes.ConclusionsLeishmania infantum promastigotes altered the characteristics of neutrophils and induced NET extrusion by activating the lipoxin A4 receptor. The lipoxin A4 receptor may have potential as a therapeutic target in relation to NET extrusion in the treatment of leishmaniasis, but its mechanisms of action need to be explored in more depth.

Highlights

Neutrophils play an immunomodulatory role through the release of neutrophil extracellular traps (NETs)
The process of NET release involves the decondensation of chromatin and the disruption of nuclear and granular architecture to allow the mixing of chromatin and antimicrobial granular content in the cytoplasm; this subsequently leads to the release of the chromatin network with anchored granular proteins, Wei et al Parasites Vectors (2019) 12:275 such as elastase and myeloperoxidase (MPO), into the extracellular space [10]
Leishmania infantum promastigotes induce the release of NETs and are trapped by NETs To confirm the potential of L. infantum to induce the formation of NETs, we cocultured L. infantum promastigotes with neutrophils for 5 h

Summary

Introduction

Neutrophils play an immunomodulatory role through the release of neutrophil extracellular traps (NETs). The process of NET release involves the decondensation of chromatin and the disruption of nuclear and granular architecture to allow the mixing of chromatin and antimicrobial granular content in the cytoplasm; this subsequently leads to the release of the chromatin network with anchored granular proteins, Wei et al Parasites Vectors (2019) 12:275 such as elastase and myeloperoxidase (MPO), into the extracellular space [10]. This novel type of cell program is called NETosis, and NETs are primarily comprised of DNA backbone fibers, antibacterial proteins/peptides, granule proteins, etc. Many aspects of the immune response to Leishmania species have been unveiled, little is known in terms of the mechanisms of activation of NETosis and the role of NETs

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