Determinants of Innate Immunity in Visceral Leishmaniasis and Their Implication in Vaccine Development.
Determinants of Innate Immunity in Visceral Leishmaniasis and Their Implication in Vaccine Development.
复制标题
DOI：
10.3389/fimmu.2021.748325
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Nakhasi HL
中科院分区：
文献类型：
--
作者：
Volpedo G;Pacheco-Fernandez T;Bhattacharya P;Oljuskin T;Dey R;Gannavaram S;Satoskar AR;Nakhasi HL
利什曼病是世界热带和亚热带地区的地方病，通过受感染的白蛉叮咬传播。利什曼原虫、宿主先天免疫细胞和适应性免疫之间的多方面相互作用决定了发病机制和疾病发展的严重程度。利什曼原虫寄生虫通过吞噬性先天免疫细胞（如中性粒细胞、巨噬细胞和树突状细胞（DC））的杀微生物功能的破坏和减弱来建立慢性感染。其他先天性细胞如炎性单核细胞、肥大细胞和NK细胞也有助于对利什曼原虫感染的抗性和/或易感性。除了来自先天免疫细胞的细胞因子/趋化因子信号外，最近的研究还确定了激活不同免疫信号级联的先天细胞代谢途径的微妙变化。代谢途径，表观遗传重编程和免疫信号级联驱动不同的先天免疫反应之间的联系，仍然是利什曼原虫发病机制的充分理解。此外，开发安全有效的利什曼病疫苗需要更广泛地了解寄生虫和先天免疫细胞之间的早期相互作用。在这篇综述中，我们专注于目前的理解先天免疫细胞的具体作用，代谢组学和表观遗传重编程和免疫调节，发生在内脏利什曼病，以及所使用的寄生虫逃避和调节宿主免疫的策略。我们强调如何利用这些途径开发安全有效的利什曼原虫疫苗。
Leishmaniasis is endemic to the tropical and subtropical regions of the world and is transmitted by the bite of an infected sand fly. The multifaceted interactions between Leishmania, the host innate immune cells, and the adaptive immunity determine the severity of pathogenesis and disease development. Leishmania parasites establish a chronic infection by subversion and attenuation of the microbicidal functions of phagocytic innate immune cells such as neutrophils, macrophages and dendritic cells (DCs). Other innate cells such as inflammatory monocytes, mast cells and NK cells, also contribute to resistance and/or susceptibility to Leishmania infection. In addition to the cytokine/chemokine signals from the innate immune cells, recent studies identified the subtle shifts in the metabolic pathways of the innate cells that activate distinct immune signal cascades. The nexus between metabolic pathways, epigenetic reprogramming and the immune signaling cascades that drive the divergent innate immune responses, remains to be fully understood in Leishmania pathogenesis. Further, development of safe and efficacious vaccines against Leishmaniasis requires a broader understanding of the early interactions between the parasites and innate immune cells. In this review we focus on the current understanding of the specific role of innate immune cells, the metabolomic and epigenetic reprogramming and immune regulation that occurs during visceral leishmaniasis, and the strategies used by the parasite to evade and modulate host immunity. We highlight how such pathways could be exploited in the development of safe and efficacious Leishmania vaccines.