Dual neutrophil subsets exacerbate or suppress inflammation in tuberculosis via IL-1ß or PD-L1.
Life Sci Alliance
; 7(7)2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38803236
ABSTRACT
Neutrophils can be beneficial or deleterious during tuberculosis (TB). Based on the expression of MHC-II and programmed death ligand 1 (PD-L1), we distinguished two functionally and transcriptionally distinct neutrophil subsets in the lungs of mice infected with mycobacteria. Inflammatory [MHC-II-, PD-L1lo] neutrophils produced inflammasome-dependent IL-1ß in the lungs in response to virulent mycobacteria and "accelerated" deleterious inflammation, which was highly exacerbated in IFN-γR-/- mice. Regulatory [MHC-II+, PD-L1hi] neutrophils "brake" inflammation by suppressing T-cell proliferation and IFN-γ production. Such beneficial regulation, which depends on PD-L1, is controlled by IFN-γR signaling in neutrophils. The hypervirulent HN878 strain from the Beijing genotype curbed PD-L1 expression by regulatory neutrophils, abolishing the braking function and driving deleterious hyperinflammation in the lungs. These findings add a layer of complexity to the roles played by neutrophils in TB and may explain the reactivation of this disease observed in cancer patients treated with anti-PD-L1.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Tuberculosis
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Interleucina-1beta
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Antígeno B7-H1
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Inflamación
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Pulmón
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Neutrófilos
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Life Sci Alliance
Año:
2024
Tipo del documento:
Article
País de afiliación:
Francia