Transitional premonocytes emerge in the periphery for host defense against bacterial infections
Ye Chean Teh, Ming Yao Chooi, Dehua Liu, Immanuel Kwok, Ghee Chuan Lai, Liyana Ayub Ow Yong, Melissa Ng, J Li, Yingrou Tan, Maximilien Evrard, Leonard Tan, Ka Hang Liong, Keith Weng Kit Leong, Chi Ching Goh, Andrew Chan, Nurhidaya Binte Shadan, Chinmay Kumar Mantri, You Yi Hwang, Hui Cheng, Tao Cheng, Weimiao Yu, Hong Liang Tey, Anis Larbi, Ashley L. St. John, Véronique Angeli, Christiane Ruedl, Bernett Lee, Florent Ginhoux, Swaine L. Chen, Lai Guan Ng, Jeak Ling Ding, Shu Zhen Chong
Abstract
Circulating Ly6C hi 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 hi 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.