Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, India.
Research & Development, Thermo Fisher Scientific, Bengaluru, Karnataka, India.
J Cell Physiol. 2021 Apr;236(4):2255-2267. doi: 10.1002/jcp.30029. Epub 2020 Dec 20.
Neutrophils with their array of microbicidal activities are the first innate immune cells to guard against infection. They are also most crucial for the host's initial defense against Leishmania parasites which cause clinically diverse diseases ranging from self-healing cutaneous leishmaniasis (CL) to a more severe visceral form, visceral leishmaniasis (VL). Neutrophils are recruited in large numbers at the infection site after bite of sandfly, which is the vector for the disease. The initial interaction of neutrophils with the parasites may modulate the subsequent innate and adaptive immune responses and hence affect the disease outcome. The purpose of this review is to comprehensively appraise the role of neutrophils during the early stages of Leishmania infection with a focus on the visceral form of the disease. In the past decade, new insights regarding the role of neutrophils in VL have surfaced which have been extensively elaborated in the present review. In addition, since much of the information regarding neutrophil-Leishmania early interaction has accumulated through studies on mouse models of CL, these studies are also revisited. We begin by reviewing the factors which drive the recruitment of neutrophils at the site of injection by the sandfly. We then discuss the studies delineating the molecular mechanisms involved in the uptake of the Leishmania parasite by neutrophils and how the parasite subverts their microbicidal functions. In the end, the interaction of infected neutrophils with macrophages and dendritic cells is summarized.
中性粒细胞具有多种杀菌活性，是抵御感染的第一道先天免疫细胞。它们对于宿主抵御利什曼原虫寄生虫的初始防御也至关重要，利什曼原虫寄生虫可引起从自限性皮肤利什曼病（CL）到更严重内脏利什曼病（VL）等临床表现多样的疾病。在沙蝇叮咬后，大量中性粒细胞被招募到感染部位，沙蝇是该疾病的传播媒介。中性粒细胞与寄生虫的最初相互作用可能调节随后的先天和适应性免疫反应，从而影响疾病结局。本综述的目的是全面评估中性粒细胞在利什曼原虫感染早期阶段的作用，重点关注内脏形式的疾病。在过去的十年中，有关中性粒细胞在 VL 中的作用的新见解已经出现，本综述对此进行了广泛阐述。此外，由于有关中性粒细胞与利什曼原虫早期相互作用的大部分信息是通过 CL 的小鼠模型研究积累的，因此也重新审视了这些研究。我们首先回顾了驱使沙蝇在注射部位招募中性粒细胞的因素。然后，我们讨论了阐明中性粒细胞摄取利什曼原虫寄生虫所涉及的分子机制的研究，以及寄生虫如何削弱其杀菌功能。最后，总结了感染的中性粒细胞与巨噬细胞和树突状细胞的相互作用。
