Accumulation of EBI3 induced by virulent Mycobacterium tuberculosis inhibits apoptosis in murine macrophages.
Pathog Dis
; 77(1)2019 02 01.
Article
em En
| MEDLINE
| ID: mdl-30753412
ABSTRACT
Macrophages are the primary host target cells of Mycobacterium tuberculosis (M. tb). As a subunit of immunoregulatory cytokines IL-27 and IL-35, Epstein-Barr virus-induced gene 3 (EBI3) has typically been explored as the secreted form and assessed in terms of its effects triggered by extracellular EBI3. However, little is known about intracellular EBI3 function. In the current study, we report that EBI3 production by macrophages is elevated in TB patients. We further demonstrate that increased EBI3 accumulates in virulent M. tb-treated murine macrophages. Eukaryotic translation elongation factor 1-alpha 1 (eEF1A1) binds to intracellular EBI3 to reduce Lys48 (K48)-linked ubiquitination of EBI3, leading to EBI3 accumulation. Moreover, the intracellular EBI3 inhibits caspase-3-mediated apoptosis in M. tb-treated macrophages. Herein, we propose a novel mechanism for accumulating intracellular EBI3 and its regulation of macrophage apoptosis in response to virulent M. tb.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tuberculose
/
Antígenos de Histocompatibilidade Menor
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Apoptose
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Receptores de Citocinas
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Macrófagos
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Mycobacterium tuberculosis
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Pathog Dis
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China