CD4+ T regulatory cells (Tregs) are a group of T lymphocytes that maintains self-tolerance and protect the host from inflammation-induced tissue damage. An interacting network of cytokines and transcription factors influence the origin, differentiation, and function of the Tregs in primary and secondary lymphoid organs. However, following antigenic stimulation, it can also be induced at the sites of infection. Immune cell resident microbial pathogens, such as Leishmania, employ varieties of mechanisms to promote the suppressive functions of Tregs for protective evasion from the host immune system. This establishes a state of immune unresponsiveness in the host, exacerbating the disease in Leishmania infection. Elimination of Leishmania pathogens is accomplished with a strong pro-inflammatory response accompanied by the release of host protective cytokines such as Interleukin-2 (IL-2), Interferon-gamma (IFN-γ), and Tumor necrosis factor-alpha (TNF-α), which functions through suppression of Tregs or making the effector cells recalcitrant to Treg mediated suppression. Nevertheless, during chronic infection, the persistence of unwarranted pro-inflammatory cytokines can trigger self-tissue damage. Tregs limit the consequence of chronic inflammation to restrict self-harm suggesting its mutually opposing role in host protection. Furthermore, Tregs function to prevent complete parasite clearance to provide long-term immunity to re-infection. This review summarizes the roles of pro-inflammatory and anti-inflammatory cytokines involved in the homing, activation, differentiation, and suppression of Tregs in the course of Leishmania infection. We also suggest cytokines that can be modulated as potential therapeutic targets to treat Leishmania infection.

中文翻译：

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利什曼病调节性 T 细胞亚群产生和功能中的细胞因子

CD4+ T 调节细胞 (Tregs) 是一组 T 淋巴细胞，可维持自身耐受性并保护宿主免受炎症诱导的组织损伤。细胞因子和转录因子的相互作用网络影响 Treg 在初级和次级淋巴器官中的起源、分化和功能。然而，在抗原刺激后，它也可以在感染部位被诱导。免疫细胞驻留微生物病原体，如利什曼原虫，采用多种机制来促进 Treg 的抑制功能，以保护性逃避宿主免疫系统。这在宿主中建立了一种免疫无反应状态，加剧了利什曼原虫感染的疾病。消除利什曼原虫病原体是通过强烈的促炎反应完成的，伴随着宿主保护性细胞因子的释放，例如白细胞介素 2 (IL-2)、干扰素-γ (IFN-γ) 和肿瘤坏死因子-α (TNF- α)，其通过抑制 Tregs 或使效应细胞对 Treg 介导的抑制产生抗拒作用。然而，在慢性感染期间，无根据的促炎细胞因子的持续存在会引发自身组织损伤。Tregs 限制慢性炎症的后果以限制自我伤害，这表明它在宿主保护中的相互对立的作用。此外，Tregs 的作用是防止完全清除寄生虫，以提供对再感染的长期免疫力。本综述总结了促炎和抗炎细胞因子在归巢、激活、在利什曼原虫感染过程中分化和抑制 Tregs。我们还建议可以调节的细胞因子作为治疗利什曼原虫感染的潜在治疗靶点。