Macrophages exploit the mannose receptor and JAK-STAT1-MHC-II pathway to drive antigen presentation and the antimycobacterial immune response after BCG vaccination.
Acta Biochim Biophys Sin (Shanghai)
; 56(8): 1130-1144, 2024 Jun 18.
Article
en En
| MEDLINE
| ID: mdl-38894685
ABSTRACT
Tuberculosis (TB), caused by Mycobacterium tuberculosis ( M. tb), remains one of the leading causes of fatal infectious diseases worldwide. The only licensed vaccine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), has variable efficacy against TB in adults. Insufficiency of immune cell function diminishes the protective effects of the BCG vaccine. It is critical to clarify the mechanism underlying the antimycobacterial immune response during BCG vaccination. Macrophage mannose receptor (MR) is important for enhancing the uptake and processing of glycoconjugated antigens from pathogens for presentation to T cells, but the roles of macrophage MR in the BCG-induced immune response against M. tb are not yet clear. Here, we discover that macrophage MR deficiency impairs the antimycobacterial immune response in BCG-vaccinated mice. Mechanistically, macrophage MR triggers JAK-STAT1 signaling, which promotes antigen presentation via upregulated MHC-II and induces IL-12 production by macrophages, contributing to CD4 + T cell activation and IFN-γ production. MR deficiency in macrophages reduces the vaccine efficacy of BCG and increases susceptibility to M. tb H37Ra challenge in mice. Our results suggest that MR is critical for macrophage antigen presentation and the antimycobacterial immune response to BCG vaccination and offer valuable guidance for the preventive strategy of BCG immunization.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Vacuna BCG
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Presentación de Antígeno
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Receptores de Superficie Celular
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Lectinas Tipo C
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Lectinas de Unión a Manosa
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Factor de Transcripción STAT1
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Quinasas Janus
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Receptor de Manosa
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Macrófagos
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Ratones Endogámicos C57BL
Límite:
Animals
Idioma:
En
Revista:
Acta Biochim Biophys Sin (Shanghai)
Asunto de la revista:
BIOFISICA
/
BIOQUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China