1. Transitional premonocytes emerge in the periphery for host defense against bacterial infections
- Author
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Ye Chean Teh, Ming Yao Chooi, Dehua Liu, Immanuel Kwok, Ghee Chuan Lai, Liyana Ayub Ow Yong, Melissa Ng, Jackson L. Y. Li, Yingrou Tan, Maximilien Evrard, Leonard Tan, Ka Hang Liong, Keith Leong, Chi Ching Goh, Andrew Y. J. Chan, Nurhidaya Binte Shadan, Chinmay Kumar Mantri, You Yi Hwang, Hui Cheng, Tao Cheng, Weimiao Yu, Hong Liang Tey, Anis Larbi, Ashley St John, Veronique Angeli, Christiane Ruedl, Bernett Lee, Florent Ginhoux, Swaine L. Chen, Lai Guan Ng, Jeak Ling Ding, Shu Zhen Chong, Lee Kong Chian School of Medicine (LKCMedicine), School of Biological Sciences, Yong Loo Lin School of Medicine, NUS, National Skin Centre, and Singapore Immunology Network (SIgN), A*STAR
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Multidisciplinary ,Macrophages ,Biological sciences [Science] ,Bacterial Infections ,Monocytes ,Mice, Inbred C57BL ,Mice ,Sepsis ,Host Defense ,Animals ,Cytokines ,Humans ,Medicine [Science] - Abstract
Circulating Ly6Chi 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 Ly6Chi 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. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) Published version This research was funded by Singapore Immunology Network (SIgN) core funding and A*STAR, Singapore. F.G. is an EMBO YIP awardee and is supported by SIgN core funding and Singapore National Research Foundation Investigatorship (NRF2016NRF-NRF1001-02). L.G.N. is supported by SIgN core funding. S.Z.C. is supported by the Ministry of Health, Singapore’s National Medical Research Council under its Open Fund-Young Individual Research Grant (OFYIRG17may036), and A*STAR Career Development Award (192D8043). Y.C.T. is a graduate scholar supported by the Ministry of Education, Singapore. M.Y.C. is a graduate scholar supported by the SIgN-NTU-NUS scholarship, Singapore. SIgN Flow Cytometry facility is supported by National Research Foundation (NRF) Singapore under Shared Infrastructure Support (SIS) (NRF2017_SISFP09).
- Published
- 2022