Malarial disease caused by Plasmodium parasites challenges the mammalian immune system with a delicate balancing act. Robust inflammatory responses are required to control parasite replication within red blood cells, which if unchecked, can lead to severe anemia and fatality. However, the same inflammatory response that controls parasite replication is also associated with immunopathology and severe disease, as is exemplified by cerebral malaria. A robust literature has identified critical roles for innate, cellular, and humoral immune responses orchestrated by IFN-γ and TH1 type responses in controlling blood stage malarial disease. In contrast, TGF-β and IL-10 have been identified as important anti-inflammatory immunomodulators that help to limit inflammation and pathology during malaria. TGF-β is a pleiotropic cytokine, with the ability to exert a wide variety of context-dependent immunomodulatory roles.The specific mechanisms that allow TGF-β to protect against malarial pathology remain essentially unexplored and offer a promising avenue to dissect the most critical elements of immunomodulation in avoiding severe malaria. Here we discuss potential immunomodulatory roles for TGF-β during malaria in light of recent advances in our understanding of the role of Tregs during blood-stage malaria.

中文翻译：

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黑匣子中的平衡：血液阶段疟疾期间TGF-β信号传导的潜在免疫调节作用。

由疟原虫寄生虫引起的疟疾疾病以微妙的平衡作用挑战了哺乳动物的免疫系统。需要强有力的炎症反应来控制红细胞内的寄生虫复制，如果不加以控制，会导致严重的贫血和死亡。但是，控制寄生虫复制的相同炎症反应也与免疫病理和严重疾病有关，例如脑疟疾。大量文献已经确定了由IFN-γ和TH1型应答共同调控的先天，细胞和体液免疫应答在控制血液阶段疟疾中的关键作用。相比之下，TGF-β和IL-10被确定为重要的抗炎免疫调节剂，有助于限制疟疾期间的炎症和病理。TGF-β是一种多效细胞因子，允许TGF-β预防疟疾病理的具体机制基本上尚未被探索，并且为解剖免疫调节中最关键的因素提供了一个有希望的途径，以避免严重的疟疾。在这里，根据我们对Tregs在血液阶段疟疾中作用的理解的最新进展，我们讨论了疟疾中TGF-β的潜在免疫调节作用。