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Emerg Microbes Infect . Time-resolved scRNA-seq reveals transcription dynamics of polarized macrophages with influenza A virus infection and antigen

tetano

Editor, Senior Moderator
Emerg Microbes Infect


. 2024 Aug 12:2387450.
doi: 10.1080/22221751.2024.2387450. Online ahead of print. Time-resolved scRNA-seq reveals transcription dynamics of polarized macrophages with influenza A virus infection and antigen presentation to T cells

Jiapei Yu[SUP] 1 2 [/SUP], Congcong Shang[SUP] 1 3 [/SUP], Xiaoyan Deng[SUP] 4 [/SUP], Ju Jia[SUP] 5 [/SUP], Xiao Shang[SUP] 4 [/SUP], Zeyi Wang[SUP] 3 [/SUP], Ying Zheng[SUP] 6 [/SUP], Rongling Zhang[SUP] 1 3 [/SUP], Yeming Wang[SUP] 1 2 [/SUP], Hui Zhang[SUP] 1 6 [/SUP], Hongyu Liu[SUP] 1 6 [/SUP], William J Liu[SUP] 7 [/SUP], Hui Li[SUP] 1 2 [/SUP], Bin Cao[SUP] 1 2 3 5 6 [/SUP]



Affiliations
Free article Abstract

AbstractThroughout 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 Arg1_macrophages is the sole state supporting successful replication of influenza A virus. Furthermore, we identified distinct antigen presentation capabilities to CD4[SUP]+[/SUP] T and CD8[SUP]+[/SUP] T cells across diverse polarized states of macrophages. Notably, the M1 phenotype, exhibited by both bone marrow-derived macrophages (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[SUP]+[/SUP] T cell differentiation progressed, M1 polarization exhibited an enhanced capacity for cross-presentation. All three phenotypes of BMDMs, including M1, demonstrated robust presentation of CD4[SUP]+[/SUP] regulatory T cells, while displaying limited ability to present naive CD4[SUP]+[/SUP] 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.

Keywords: antigen presentation; influenza A virus; polarized macrophages; specific T cell response; time-resolved.

 
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