Phospholipase C epsilon-1 (PLCÆ1) mediates macrophage activation and protection against tuberculosis.
Infect Immun
; 92(4): e0049523, 2024 Apr 09.
Article
em En
| MEDLINE
| ID: mdl-38451080
ABSTRACT
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infects up to a quarter of the world's population. Although immune responses can control Mtb infection, 5%-10% of infected individuals can progress to active TB disease (progressors). A myriad of host factors regulate disease progression in TB and a better understanding of immune correlates of protection and disease is pivotal for the development of new therapeutics. Comparison of human whole blood transcriptomic metadata with that of macaque TB progressors and Mtb-infected diversity outbred mice (DO) led to the identification of differentially regulated gene (DEG) signatures, associated with TB progression or control. The current study assessed the function of Phospholipase C epsilon (PLCÆ1), the top downregulated gene across species in TB progressors, using a gene-specific knockout mouse model of Mtb infection and in vitro Mtb-infected bone marrow-derived macrophages. PLCÆ1 gene expression was downregulated in TB progressors across species. PLCε1 deficiency in the mouse model resulted in increased susceptibility to Mtb infection, coincident accumulation of lung myeloid cells, and reduced ability to mount antibacterial responses. However, PLCε1 was not required for the activation and accumulation of T cells in mice. Our results suggest an important early role for PLCÆ1 in shaping innate immune response to TB and may represent a putative target for host-directed therapy.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Tuberculose
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Fosfoinositídeo Fosfolipase C
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Mycobacterium tuberculosis
Limite:
Animals
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Humans
Idioma:
En
Revista:
Infect Immun
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos