Frontline Science: Leishmania mexicana amastigotes can replicate within neutrophils
Frontline Science: Leishmania mexicana amastigotes can replicate within neutrophils
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DOI：
10.1189/jlb.4hi0417-158r
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发表时间：
2017-11-01
影响因子：
5.5
通讯作者：
Tacchini-Cottier, Fabienne
中科院分区：
文献类型：
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作者：
Hurrell, Benjamin P.;Beaumann, Manon;Tacchini-Cottier, Fabienne
L.墨西哥原生动物寄生虫可以在中性粒细胞内复制。皮肤利什曼病是一种被忽视的热带疾病，引起一系列的临床表现，从自愈到不愈合的病变，可能是非常难以治疗的。当寄生虫处于非复制的前鞭毛体形式时。中性粒细胞也已检测到在感染的后期阶段，在不愈合的慢性皮肤病变。然而，这些细胞和复制细胞内无鞭毛体形式的寄生虫之间的相互作用研究甚少。在这里，我们表明，利什曼原虫无鞭毛体被有效地内化的中性粒细胞，这个过程只有一个低的影响中性粒细胞活化和凋亡。在中性粒细胞中，无鞭毛体存在于酸化的囊泡中。此外，在皮肤未愈合病变中，发现严重感染的中性粒细胞，每个细胞多达6个寄生虫。为了研究无鞭毛体是否可以在中性粒细胞内复制，我们产生了光转换荧光寄生虫。利用流式细胞术成像和延时显微镜，我们可以证明，一个子集的寄生虫内复制中性粒细胞。总的来说，我们的数据揭示了中性粒细胞的一个新作用，它可以在感染的慢性阶段作为寄生虫复制的小生境，从而促进疾病的病理学。
L. mexicana protozoan parasites can replicate within neutrophils. Cutaneous leishmaniasis is a neglected tropical disease, causing a spectrum of clinical manifestations varying from self-healing to unhealing lesions that may be very difficult to treat. Emerging evidence points to a detrimental role for neutrophils during the first hours following infection with many distinct Leishmania species (spp.) at a time when the parasite is in its nonreplicative promastigote form. Neutrophils have also been detected at later stages of infection in unhealing chronic cutaneous lesions. However, the interactions between these cells and the replicative intracellular amastigote form of the parasite have been poorly studied. Here, we show that Leishmaniamexicana amastigotes are efficiently internalized by neutrophils and that this process has only a low impact on neutrophil activation and apoptosis. In neutrophils, the amastigotes were found in acidified vesicles. Furthermore, within cutaneous unhealing lesions, heavily infected neutrophils were found with up to 6 parasites per cell. To investigate if the amastigotes could replicate within neutrophils, we generated photoconvertible fluorescent parasites. With the use of flow cytometry imaging and time-lapse microscopy, we could demonstrate that a subset of parasites replicated within neutrophils. Overall, our data reveal a novel role for neutrophils that can act as a niche for parasite replication during the chronic phase of infection, thereby contributing to disease pathology.