Hannover Medical School, Institute of Medical Microbiology and Hospital Epidemiology, Hannover, Germany.
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Front Immunol. 2019 Feb 14;10:242. doi: 10.3389/fimmu.2019.00242. eCollection 2019.
is a widespread parasitic pathogen that infects over one third of the global human population. The parasite invades and chronically persists in the central nervous system (CNS) of the infected host. Parasite spread and persistence is intimately linked to an ensuing immune response, which does not only limit parasite-induced damage but also may facilitate dissemination and induce parasite-associated immunopathology. Here, we discuss various aspects of toxoplasmosis where knowledge is scarce or controversial and, the recent advances in the understanding of the delicate interplay of with the immune system in experimental and clinical settings. This includes mechanisms for parasite passage from the circulation into the brain parenchyma across the blood-brain barrier during primary acute infection. Later, as chronic latent infection sets in with control of the parasite in the brain parenchyma, the roles of the inflammatory response and of immune cell responses in this phase of the disease are discussed. Additionally, the function of brain resident cell populations is delineated, i.e., how neurons, astrocytes and microglia serve both as target cells for the parasite but also actively contribute to the immune response. As the infection can reactivate in the CNS of immune-compromised individuals, we bring up the immunopathogenesis of reactivated toxoplasmosis, including the special case of congenital CNS manifestations. The relevance, advantages and limitations of rodent infection models for the understanding of human cerebral toxoplasmosis are discussed. Finally, this review pinpoints questions that may represent challenges to experimental and clinical science with respect to improved diagnostics, pharmacological treatments and immunotherapies.
刚地弓形虫是一种广泛存在的寄生虫病原体，感染了全球超过三分之一的人口。该寄生虫入侵并在受感染宿主的中枢神经系统（CNS）中慢性持续存在。寄生虫的传播和持续存在与随之而来的免疫反应密切相关，这种免疫反应不仅限制了寄生虫引起的损伤，还可能促进寄生虫的传播并诱导与寄生虫相关的免疫病理学。在这里，我们讨论了弓形虫病的各个方面，这些方面的知识要么匮乏，要么存在争议，以及在实验和临床环境中，人们对弓形虫与免疫系统之间微妙相互作用的最新理解。这包括寄生虫从循环系统穿过血脑屏障进入脑实质的过程中的各种机制，在原发性急性感染期间。后来，随着慢性潜伏感染的发生，寄生虫在脑实质中得到控制，炎症反应和免疫细胞反应在疾病的这一阶段的作用将被讨论。此外，还将描述脑内常驻细胞群体的功能，即神经元、星形胶质细胞和小胶质细胞如何既是寄生虫的靶细胞，又积极参与免疫反应。由于感染可能在免疫功能低下个体的中枢神经系统中重新激活，我们将提到重新激活的弓形虫病的免疫发病机制，包括先天性中枢神经系统表现的特殊情况。讨论了啮齿动物感染模型对理解人类大脑弓形虫病的相关性、优势和局限性。最后，本综述指出了可能对实验和临床科学提出挑战的问题，涉及改进的诊断、药物治疗和免疫疗法。
