Leishmania amazonensis Amastigotes Trigger Neutrophil Activation but Resist Neutrophil Microbicidal Mechanisms
Leishmania amazonensis Amastigotes Trigger Neutrophil Activation but Resist Neutrophil Microbicidal Mechanisms
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DOI：
10.1128/iai.00770-13
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发表时间：
2013-11-01
影响因子：
3.1
通讯作者：
Soong, Lynn
中科院分区：
文献类型：
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作者：
Carlsen, Eric D.;Hay, Christie;Soong, Lynn
中性粒细胞是第一个渗透到利什曼原虫感染部位的细胞，这些细胞有助于在感染开始后不久减轻寄生虫负担。一些临床报告表明，中性粒细胞在利什曼病过程中持续募集，并且从慢性感染患者和实验感染动物中分离出了带有无鞭虫的中性粒细胞。本研究的目的是比较巯基乙酸盐诱导的小鼠中性粒细胞对亚马逊乳杆菌单环原乳糜虫和无尾乳糜虫的反应，这些无尾乳糜虫来源于无菌培养物或感染小鼠的病变。中性粒细胞有效地内化了寄生虫的无马鞭毛体和原马鞭毛体形式，并且在脂多糖（LPS）激活的中性粒细胞中或在感染小鼠的血清中被寄生虫活化时，吞噬作用增强。寄生虫摄取导致中性粒细胞活化、氧化破裂和加速中性粒细胞死亡。虽然原乳突菌触发肿瘤坏死因子α (tnf - α)的释放，但对无尾乳突菌的摄取优先导致中性粒细胞分泌白细胞介素-10 （IL-10）。最后，大多数原生无尾线虫被中性粒细胞杀死，而无菌培养和病变来源的无尾线虫对中性粒细胞杀微生物机制具有高度抗性。本研究表明中性粒细胞对promastigote和amastigote感染表现出不同的反应。我们的研究结果对确定皮肤利什曼病晚期持续中性粒细胞募集和中性粒细胞-无梭菌相互作用的影响具有重要意义。
Neutrophils are the first cells to infiltrate to the site of Leishmania promastigote infection, and these cells help to reduce parasite burden shortly after infection is initiated. Several clinical reports indicate that neutrophil recruitment is sustained over the course of leishmaniasis, and amastigote-laden neutrophils have been isolated from chronically infected patients and experimentally infected animals. The goal of this study was to compare how thioglycolate-elicited murine neutrophils respond to L. amazonensis metacyclic promastigotes and amastigotes derived from axenic cultures or from the lesions of infected mice. Neutrophils efficiently internalized both amastigote and promastigote forms of the parasite, and phagocytosis was enhanced in lipopolysaccharide (LPS)-activated neutrophils or when parasites were opsonized in serum from infected mice. Parasite uptake resulted in neutrophil activation, oxidative burst, and accelerated neutrophil death. While promastigotes triggered the release of tumor necrosis factor alpha (TNF-alpha), uptake of amastigotes preferentially resulted in the secretion of interleukin-10 (IL-10) from neutrophils. Finally, the majority of promastigotes were killed by neutrophils, while axenic culture- and lesion-derived amastigotes were highly resistant to neutrophil microbicidal mechanisms. This study indicates that neutrophils exhibit distinct responses to promastigote and amastigote infection. Our findings have important implications for determining the impact of sustained neutrophil recruitment and amastigote-neutrophil interactions during the late phase of cutaneous leishmaniasis.