Teh Ye Chean, Chooi Ming Yao, Liu Dehua, Kwok Immanuel, Lai Ghee Chuan, Ayub Ow Yong Liyana, Ng Melissa, Li Jackson L Y, Tan Yingrou, Evrard Maximilien, Tan Leonard, Liong Ka Hang, Leong Keith, Goh Chi Ching, Chan Andrew Y J, Shadan Nurhidaya Binte, Mantri Chinmay Kumar, Hwang You Yi, Cheng Hui, Cheng Tao, Yu Weimiao, Tey Hong Liang, Larbi Anis, St John Ashley, Angeli Veronique, Ruedl Christiane, Lee Bernett, Ginhoux Florent, Chen Swaine L, Ng Lai Guan, Ding Jeak Ling, Chong Shu Zhen
Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, Singapore 138648, Singapore.
Department of Biological Science, National University of Singapore (NUS), Singapore 117543, Singapore.
Sci Adv. 2022 Mar 4;8(9):eabj4641. doi: 10.1126/sciadv.abj4641.
Circulating Ly6C monocytes often undergo cellular death upon exhaustion of their antibacterial effector functions, which limits their capacity for subsequent macrophage differentiation. This shrouds the understanding on how the host replaces the tissue-resident macrophage niche effectively during bacterial invasion to avert infection morbidity. Here, we show that proliferating transitional premonocytes (TpMos), an immediate precursor of mature Ly6C monocytes (MatMos), were mobilized into the periphery in response to acute bacterial infection and sepsis. TpMos were less susceptible to apoptosis and served as the main source of macrophage replenishment when MatMos were vulnerable toward bacteria-induced cellular death. Furthermore, TpMo and its derived macrophages contributed to host defense by balancing the proinflammatory cytokine response of MatMos. Consequently, adoptive transfer of TpMos improved the survival outcome of lethal sepsis. Our findings hence highlight a protective role for TpMos during bacterial infections and their contribution toward monocyte-derived macrophage heterogeneity in distinct disease outcomes.
循环中的Ly6C单核细胞在其抗菌效应功能耗竭后常发生细胞死亡，这限制了它们随后分化为巨噬细胞的能力。这使得人们难以理解宿主在细菌入侵期间如何有效地替代组织驻留巨噬细胞龛以避免感染发病。在此，我们表明，增殖性过渡前单核细胞（TpMos）是成熟Ly6C单核细胞（MatMos）的直接前体，在急性细菌感染和脓毒症时被动员到外周。当MatMos易受细菌诱导的细胞死亡影响时，TpMos对凋亡的敏感性较低，并作为巨噬细胞补充的主要来源。此外，TpMo及其衍生的巨噬细胞通过平衡MatMos的促炎细胞因子反应来促进宿主防御。因此，过继转移TpMos改善了致死性脓毒症的生存结果。我们的研究结果因此突出了TpMos在细菌感染期间的保护作用及其对不同疾病结局中单核细胞衍生巨噬细胞异质性的贡献。
