Time-resolved scRNA-seq reveals transcription dynamics of polarized macrophages with influenza A virus infection and antigen presentation to T cells

• Published in: Emerging microbes & infections Vol. 13; no. 1; p. 2387450
• Main Authors: Yu, Jiapei, Shang, Congcong, Deng, Xiaoyan, Jia, Ju, Shang, Xiao, Wang, Zeyi, Zheng, Ying, Zhang, Rongling, Wang, Yeming, Zhang, Hui, Liu, Hongyu, Liu, William J, Li, Hui, Cao, Bin
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.12.2024; Taylor & Francis Group
• Subjects: Animals; Antigen Presentation; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Emerging Seasonal and Pandemic Influenza Infections; Influenza A virus; Influenza A virus - genetics; Influenza A virus - immunology; Macrophages - immunology; Macrophages - virology; Mice; Mice, Inbred C57BL; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - virology; polarized macrophages; RNA-Seq - methods; Single-Cell Analysis - methods; Single-Cell Gene Expression Analysis; specific T cell response; time-resolved; polarized macrophages; Influenza A virus; antigen presentation; time-resolved; specific T cell response
• ISSN: 2222-1751; 2222-1751
• DOI: 10.1080/22221751.2024.2387450

Throughout history, the influenza A virus has caused numerous devastating global pandemics. Macrophages, as pivotal innate immune cells, exhibit a wide range of immune functions characterized by distinct polarization states, reflecting their intricate heterogeneity. In this study, we employed the time-resolved single-cell sequencing technique coupled with metabolic RNA labelling to elucidate the dynamic transcriptional changes in distinct polarized states of bone marrow-derived macrophages (BMDMs) upon infection with the influenza A virus. Our approach not only captures the temporal dimension of transcriptional activity, which is lacking in conventional scRNA-seq methods, but also reveals that M2-polarized _macrophage cluster is the sole state supporting successful replication of influenza A virus. Furthermore, we identified distinct antigen presentation capabilities to CD4 T and CD8 T cells across diverse polarized states of macrophages. Notably, the M1 phenotype, exhibited by (BMDMs) and murine alveolar macrophages (AMs), demonstrated superior conventional and cross-presentation abilities for exogenous antigens, with a particular emphasis on cross-presentation capacity. Additionally, as CD8 T cell differentiation progressed, M1 polarization exhibited an enhanced capacity for cross-presentation. All three phenotypes of BMDMs, including M1, demonstrated robust presentation to CD4 regulatory T cells, while displaying limited ability to present to naive CD4 T cells. These findings offer novel insights into the immunological regulatory mechanisms governing distinct polarized states of macrophages, particularly their roles in restricting the replication of influenza A virus and modulating antigen-specific T cell responses through innate immunity.