Time-resolved scRNA-seq reveals transcription dynamics of polarized macrophages with influenza A virus infection and antigen presentation to T cells.
Emerg Microbes Infect
; 13(1): 2387450, 2024 Dec.
Article
en En
| MEDLINE
| ID: mdl-39129565
ABSTRACT
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 Arg1_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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Virus de la Influenza A
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Presentación de Antígeno
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Infecciones por Orthomyxoviridae
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Linfocitos T CD8-positivos
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Macrófagos
Límite:
Animals
Idioma:
En
Revista:
Emerg Microbes Infect
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Estados Unidos