National Centre for Cell Science, Ganeshkhind, Pune 411007, Maharashtra, India; Trident Academy of Creative Technology, Bhubaneshwar 751024, Odisha, India; BLDE University, Vijayapur, Karnataka, India.
Microbiology and Infection Research Domain (MIRD), Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Cytokine. 2021 Sep;145:155320. doi: 10.1016/j.cyto.2020.155320. Epub 2020 Oct 27.
Cytokines are key mediators of immune responses to autoantigens, tumor antigens and foreign antigens including pathogens and transplant antigens. The cytokines are produced by a variety of immune and non-immune cells and are dynamically regulated. Remarkably, during toxic and septic shock syndromes, anaphylactic shock and in certain viral infections supra-physiologic levels of cytokine storms are produced culminating in multi-organ failure and death. However, Leishmania infection is a chronic parasitic infection with alternate outcomes- healing or non-healing. Leishmania invades macrophages and inflicts the complex of diseases called Leishmaniases. Depending on the species of Leishmania and the organs affected, the diseases are categorized into Cutaneous Leishmaniasis (CL), Muco-cutaneous Leishmaniasis (MCL) and Visceral Leishmaniasis (VL). After successful chemotherapy of VL, a dermal manifestation- termed post-kalazar dermal leishmaniasis (PKDL)- of the same infection occurs in some patients. The operational frameworks for different cytokines have been laid to discuss how these immune mediators control each of these forms of leishmaniases. One of these frameworks is the regulation of monocytopoiesis including the role of macrophages subsets and thrombopoiesis in leishmaniases. Macrophage metabolism is linked to different cytokines and is thereby associated with the manifestation of the resistance or susceptibility to Leishmania infection and of drug resistance. The chemokine-regulated immune cell movements present the landscape of infection and pathogenesis. T cells subsets- the IFN-γ-secreting Ly6C + T cells and the regulatory T cell subsets- provide the initial skewing of Th cell subset and regulation of effector Th subsets, respectively, eventually deciding the outcome of infection.
细胞因子是针对自身抗原、肿瘤抗原和包括病原体和移植抗原在内的外来抗原的免疫反应的关键介质。细胞因子由各种免疫和非免疫细胞产生，并受到动态调节。值得注意的是，在中毒性和脓毒性休克综合征、过敏性休克以及某些病毒感染中，会产生超生理水平的细胞因子风暴，最终导致多器官衰竭和死亡。然而，利什曼原虫感染是一种慢性寄生虫感染，其结果有治愈和不治愈之分。利什曼原虫侵入巨噬细胞，并引发一系列疾病，称为利什曼病。根据利什曼原虫的种类和受影响的器官，疾病分为皮肤利什曼病（CL）、黏膜皮肤利什曼病（MCL）和内脏利什曼病（VL）。在成功治疗内脏利什曼病后，一些患者会出现同一种感染的皮肤表现，即卡拉扎尔后皮肤利什曼病（PKDL）。为了讨论这些免疫介质如何控制每种利什曼病，已经制定了针对不同细胞因子的操作框架。其中一个框架是单核细胞生成的调节，包括巨噬细胞亚群和血小板生成在利什曼病中的作用。巨噬细胞代谢与不同的细胞因子有关，因此与对利什曼原虫感染的抵抗或易感性以及耐药性的表现有关。趋化因子调节的免疫细胞运动呈现出感染和发病机制的全貌。T 细胞亚群——IFN-γ 分泌的 Ly6C+T 细胞和调节性 T 细胞亚群——分别为 Th 细胞亚群的初始倾斜和效应 Th 细胞亚群的调节提供了初始倾斜和调节，最终决定了感染的结果。
