Schanz Madison L, Zhao Fengdi, Zadeii Kamryn E, Chen Li, López-Yglesias Américo H
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States.
Department of Biostatistics, University of Florida, Tallahassee, FL, United States.
Immunohorizons. 2025 Aug 25;9(9). doi: 10.1093/immhor/vlaf037.
The obligate intracellular protozoan pathogen Toxoplasma gondii is estimated to infect a third of the world's population. Toxoplasmosis is considered a significant worldwide disease that can lead to morbidity or death in immunocompromised individuals. Host defense against T. gondii has been demonstrated to be dependent on a rapid myeloid cell and lymphocyte response working in concert to quickly eliminate the invading pathogen. Classically, T-bet-dependent group 1 innate lymphocytes (ILC1s), natural killer (NK) cells, and CD4+ T cell-derived interferon-γ (IFN-γ) are considered indispensable for host resistance against T. gondii. However, recent discoveries have illustrated that T-bet is not required for NK cell- or CD4+ T cell-derived IFN-γ. Yet, lack of T-bet still results in rapid mortality, pointing to a T-bet-dependent myeloid cell-mediated host defense pathway. This review summarizes the myeloid cell-mediated immune response against T. gondii and provides insights into the lesser known components of the T-bet-dependent myeloid cell-dependent host defense pathway for pathogen clearance.
专性细胞内原生动物病原体刚地弓形虫估计感染了世界三分之一的人口。弓形虫病被认为是一种在全球范围内具有重要影响的疾病，可导致免疫功能低下个体发病或死亡。已证明宿主对刚地弓形虫的防御依赖于快速的髓系细胞和淋巴细胞协同反应，以迅速清除入侵的病原体。传统上，T-bet依赖的1型固有淋巴细胞（ILC1）、自然杀伤（NK）细胞和CD4+ T细胞衍生的干扰素-γ（IFN-γ）被认为是宿主抵抗刚地弓形虫所不可或缺的。然而，最近的发现表明，NK细胞或CD4+ T细胞衍生的IFN-γ并不需要T-bet。然而，缺乏T-bet仍会导致快速死亡，这表明存在一条T-bet依赖的髓系细胞介导的宿主防御途径。本综述总结了髓系细胞介导的针对刚地弓形虫的免疫反应，并深入探讨了T-bet依赖的髓系细胞依赖性宿主防御途径中鲜为人知的病原体清除成分。
