Type I Interferon Signaling Regulates Ly6Chi Monocytes and Neutrophils during Acute Viral Pneumonia in Mice

PLoS Pathogens

Baik Lin Seong¹  Satoshi Uematsu¹  Mi-Na Kweon²  Shizuo Akira²  Young-Ho Byun³  Hyun-Jeong Ko⁴  Sang-Uk Seo⁴  Hyung-Joon Kwon⁴ 

[1] Department of Biotechnology, College of Engineering, Yonsei University, Seoul, South Korea;Laboratory of Host Defense, World Premier International Immunology Frontier Research Center, and Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan;Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, South Korea;Mucosal Immunology Section, International Vaccine Institute, Seoul, South Korea

关键词: Monocytes;    Neutrophils;    Influenza;    Inflammation;    Influenza viruses;    Cell differentiation;    Chemokines;    Respiratory infections;   

DOI  :  10.1371/journal.ppat.1001304

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Type I interferon (IFN-I) plays a critical role in the homeostasis of hematopoietic stem cells and influences neutrophil influx to the site of inflammation. IFN-I receptor knockout (Ifnar1−/−) mice develop significant defects in the infiltration of Ly6Chi monocytes in the lung after influenza infection (A/PR/8/34, H1N1). Ly6Chi monocytes of wild-type (WT) mice are the main producers of MCP-1 while the alternatively generated Ly6Cint monocytes of Ifnar1−/− mice mainly produce KC for neutrophil influx. As a consequence, Ifnar1−/− mice recruit more neutrophils after influenza infection than do WT mice. Treatment of IFNAR1 blocking antibody on the WT bone marrow (BM) cells in vitro failed to differentiate into Ly6Chi monocytes. By using BM chimeric mice (WT BM into Ifnar1−/− and vice versa), we confirmed that IFN-I signaling in hematopoietic cells is required for the generation of Ly6Chi monocytes. Of note, WT BM reconstituted Ifnar1−/− chimeric mice with increased numbers of Ly6Chi monocytes survived longer than influenza-infected Ifnar1−/− mice. In contrast, WT mice that received Ifnar1−/− BM cells with alternative Ly6Cint monocytes and increased numbers of neutrophils exhibited higher mortality rates than WT mice given WT BM cells. Collectively, these data suggest that IFN-I contributes to resistance of influenza infection by control of monocytes and neutrophils in the lung.

【 授权许可】

CC BY