暴露于巴西利什曼原虫会引发中性粒细胞的激活和凋亡。
Exposure to Leishmania braziliensis triggers neutrophil activation and apoptosis.
作者信息
Falcão Sarah A C, Weinkopff Tiffany, Hurrell Benjamin P, Celes Fabiana S, Curvelo Rebecca P, Prates Deboraci B, Barral Aldina, Borges Valeria M, Tacchini-Cottier Fabienne, de Oliveira Camila I
机构信息
Centro de Pesquisas Gonçalo Moniz, FIOCRUZ, Salvador, Bahia, Brazil.
Department of Biochemistry, and WHO-Immunology Research and Training Center, University of Lausanne, Epalinges, Switzerland.
出版信息
PLoS Negl Trop Dis. 2015 Mar 10;9(3):e0003601. doi: 10.1371/journal.pntd.0003601. eCollection 2015 Mar.
BACKGROUND
Neutrophils are the first line of defense against invading pathogens and are rapidly recruited to the sites of Leishmania inoculation. During Leishmania braziliensis infection, depletion of inflammatory cells significantly increases the parasite load whereas co-inoculation of neutrophils plus L. braziliensis had an opposite effect. Moreover, the co-culture of infected macrophages and neutrophils also induced parasite killing leading us to ask how neutrophils alone respond to an L. braziliensis exposure. Herein we focused on understanding the interaction between neutrophils and L. braziliensis, exploring cell activation and apoptotic fate.
METHODS AND FINDINGS
Inoculation of serum-opsonized L. braziliensis promastigotes in mice induced neutrophil accumulation in vivo, peaking at 24 h. In vitro, exposure of thyoglycollate-elicited inflammatory or bone marrow neutrophils to L. braziliensis modulated the expression of surface molecules such as CD18 and CD62L, and induced the oxidative burst. Using mCherry-expressing L. braziliensis, we determined that such effects were mainly observed in infected and not in bystander cells. Neutrophil activation following contact with L. braziliensis was also confirmed by the release of TNF-α and neutrophil elastase. Lastly, neutrophils infected with L. braziliensis but not with L. major displayed markers of early apoptosis.
CONCLUSIONS
We show that L. braziliensis induces neutrophil recruitment in vivo and that neutrophils exposed to the parasite in vitro respond through activation and release of inflammatory mediators. This outcome may impact on parasite elimination, particularly at the early stages of infection.
背景
中性粒细胞是抵御入侵病原体的第一道防线,可迅速募集至利什曼原虫接种部位。在巴西利什曼原虫感染期间,炎性细胞的耗竭会显著增加寄生虫负荷,而中性粒细胞与巴西利什曼原虫共同接种则产生相反效果。此外,感染的巨噬细胞与中性粒细胞的共培养也可诱导寄生虫杀伤,这促使我们探究中性粒细胞单独暴露于巴西利什曼原虫时的反应。在此,我们着重于理解中性粒细胞与巴西利什曼原虫之间的相互作用,探索细胞活化及凋亡命运。
方法与结果
给小鼠接种经血清调理的巴西利什曼原虫前鞭毛体可在体内诱导中性粒细胞聚集,于24小时达到峰值。在体外,将经巯基乙酸盐诱导的炎性或骨髓中性粒细胞暴露于巴西利什曼原虫,可调节诸如CD18和CD62L等表面分子的表达,并诱导氧化爆发。使用表达mCherry的巴西利什曼原虫,我们确定此类效应主要在受感染细胞而非旁观者细胞中观察到。接触巴西利什曼原虫后中性粒细胞的活化也通过肿瘤坏死因子-α和中性粒细胞弹性蛋白酶的释放得以证实。最后,感染巴西利什曼原虫而非硕大利什曼原虫的中性粒细胞显示出早期凋亡标志物。
结论
我们表明巴西利什曼原虫在体内诱导中性粒细胞募集,且体外暴露于该寄生虫的中性粒细胞通过炎性介质的活化和释放做出反应。这一结果可能影响寄生虫清除,尤其是在感染早期。