Center for Immunity and Inflammation, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, NJ, USA; Department of Medicine, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, NJ, USA.
Center for Immunity and Inflammation, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, NJ, USA; Department of Pathology, Immunology, and Laboratory Medicine, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, NJ, USA.
Cell Rep. 2022 Jan 11;38(2):110215. doi: 10.1016/j.celrep.2021.110215.
Macrophages are known to mediate anti-helminth responses, but it remains uncertain which subsets are involved or how macrophages actually kill helminths. Here, we show rapid monocyte recruitment to the lung after infection with the nematode parasite Nippostrongylus brasiliensis. In this inflamed tissue microenvironment, these monocytes differentiate into an alveolar macrophage (AM)-like phenotype, expressing both SiglecF and CD11c, surround invading parasitic larvae, and preferentially kill parasites in vitro. Monocyte-derived AMs (Mo-AMs) express type 2-associated markers and show a distinct remodeling of the chromatin landscape relative to tissue-derived AMs (TD-AMs). In particular, they express high amounts of arginase-1 (Arg1), which we demonstrate mediates helminth killing through L-arginine depletion. These studies indicate that recruited monocytes are selectively programmed in the pulmonary environment to express AM markers and an anti-helminth phenotype.
巨噬细胞被认为介导抗寄生虫反应，但仍不确定涉及哪些亚群，以及巨噬细胞实际上如何杀死寄生虫。在这里，我们显示在感染旋毛虫寄生虫巴西日圆线虫后，单核细胞迅速募集到肺部。在这个炎症组织微环境中，这些单核细胞分化为肺泡巨噬细胞（AM）样表型，表达 SiglecF 和 CD11c，包围入侵的寄生虫幼虫，并优先在体外杀死寄生虫。单核细胞衍生的 AM（Mo-AMs）表达 2 型相关标志物，并表现出与组织衍生的 AM（TD-AMs）相比染色质景观的明显重塑。特别是，它们表达大量的精氨酸酶 1（Arg1），我们证明通过精氨酸耗尽介导寄生虫杀伤。这些研究表明，募集的单核细胞在肺环境中被选择性编程以表达 AM 标志物和抗寄生虫表型。
