Girgis Natasha M, Gundra Uma Mahesh, Ward Lauren N, Cabrera Mynthia, Frevert Ute, Loke P'ng
Department of Microbiology, New York University School of Medicine, New York, New York, United States of America.
PLoS Pathog. 2014 Jun 26;10(6):e1004080. doi: 10.1371/journal.ppat.1004080. eCollection 2014 Jun.
Alternatively activated macrophages (AAM) that accumulate during chronic T helper 2 inflammatory conditions may arise through proliferation of resident macrophages or recruitment of monocyte-derived cells. Liver granulomas that form around eggs of the helminth parasite Schistosoma mansoni require AAM to limit tissue damage. Here, we characterized monocyte and macrophage dynamics in the livers of infected CX3CR1(GFP/+) mice. CX₃CR1-GFP⁺ monocytes and macrophages accumulated around eggs and in granulomas during infection and upregulated PD-L2 expression, indicating differentiation into AAM. Intravital imaging of CX₃CR1-GFP⁺ Ly6C(low) monocytes revealed alterations in patrolling behavior including arrest around eggs that were not encased in granulomas. Differential labeling of CX₃CR1-GFP⁺ cells in the blood and the tissue showed CD4⁺ T cell dependent accumulation of PD-L2⁺ CX₃CR1-GFP⁺ AAM in the tissues as granulomas form. By adoptive transfer of Ly6C(high) and Ly6C(low) monocytes into infected mice, we found that AAM originate primarily from transferred Ly6C(high) monocytes, but that these cells may transition through a Ly6C(low) state and adopt patrolling behavior in the vasculature. Thus, during chronic helminth infection AAM can arise from recruited Ly6C(high) monocytes via help from CD4⁺ T cells.
在慢性辅助性T细胞2型炎症状态下积累的替代性活化巨噬细胞（AAM）可能通过驻留巨噬细胞的增殖或单核细胞衍生细胞的募集产生。曼氏血吸虫这种蠕虫寄生虫的虫卵周围形成的肝肉芽肿需要AAM来限制组织损伤。在此，我们对感染的CX3CR1（GFP/+）小鼠肝脏中的单核细胞和巨噬细胞动态变化进行了表征。在感染期间，CX₃CR1-GFP⁺单核细胞和巨噬细胞在虫卵周围和肉芽肿中积累，并上调PD-L2表达，表明分化为AAM。对CX₃CR1-GFP⁺Ly6C（低）单核细胞进行活体成像显示其巡逻行为发生改变，包括在未被肉芽肿包裹的虫卵周围停滞。对血液和组织中的CX₃CR1-GFP⁺细胞进行差异标记显示，随着肉芽肿形成，组织中PD-L2⁺CX₃CR1-GFP⁺AAM的积累依赖于CD4⁺T细胞。通过将Ly6C（高）和Ly6C（低）单核细胞过继转移到感染小鼠体内，我们发现AAM主要源自转移的Ly6C（高）单核细胞，但这些细胞可能会经历Ly6C（低）状态并在脉管系统中采取巡逻行为。因此，在慢性蠕虫感染期间，AAM可通过CD4⁺T细胞的帮助从募集的Ly6C（高）单核细胞产生。
