Leishmania infantum Axenic Amastigotes Induce Human Neutrophil Extracellular Traps and Resist NET-Mediated Killing

Tropical Medicine and Infectious Disease

article

Thamara K. F. Oliveira¹  Jullyanna Oliveira-Silva¹  Leandra Linhares-Lacerda¹  Vanderlei da Silva Fraga-Junior²  Claudia F. Benjamim²  Anderson B. Guimaraes-Costa¹  Elvira M. Saraiva¹ 

[1] Laboratório de Imunologia das Leishmanioses, Instituto de Microbiologia Paulo de Góes, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro;Laboratório de Imunologia Molecular e Celular, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro

关键词: NETs;    Leishmania;    neutrophils;    signaling pathways;    ROS;    parasites;    innate immunity;   

DOI  :  10.3390/tropicalmed8070336

学科分类：社会科学、人文和艺术（综合）

来源: mdpi

【 摘 要 】

Neutrophils are multifaceted cells that, upon activation, release meshes of chromatin associated with different proteins, known as neutrophil extracellular traps (NETs). Leishmania amazonensis promastigotes and amastigotes induce NET release, and we have identified the signaling pathways involved in NET extrusion activated by promastigotes. Amastigotes maintain the infection in vertebrate hosts, and we have shown the association of NETs with amastigotes in human biopsies of cutaneous leishmaniasis. However, the interaction of amastigotes and neutrophils remains poorly understood. Our study aimed to characterize the pathways involved in the formation of NETs induced by axenic amastigotes from L. infantum, the causal agent of visceral leishmaniasis. Human neutrophils pretreated with signaling pathway inhibitors were incubated with amastigotes, and NET release was quantified in the culture supernatant. Amastigote viability was checked after incubation with NETs. We found that the release of NETs by neutrophils stimulated with these amastigotes requires the participation of elastase and peptidyl arginine deaminase and the involvement of PI3K, ROS, and calcium. Moreover, amastigotes are not susceptible to NET-mediated killing. Altogether, these findings improve our comprehension of the signaling pathways implicated in the interaction between amastigotes and human neutrophils.

【 授权许可】

CC BY