Peroxisomal ROS control cytosolic Mycobacterium tuberculosis replication in human macrophages.
J Cell Biol
; 222(12)2023 12 04.
Article
en En
| MEDLINE
| ID: mdl-37737955
ABSTRACT
Peroxisomes are organelles involved in many metabolic processes including lipid metabolism, reactive oxygen species (ROS) turnover, and antimicrobial immune responses. However, the cellular mechanisms by which peroxisomes contribute to bacterial elimination in macrophages remain elusive. Here, we investigated peroxisome function in iPSC-derived human macrophages (iPSDM) during infection with Mycobacterium tuberculosis (Mtb). We discovered that Mtb-triggered peroxisome biogenesis requires the ESX-1 type 7 secretion system, critical for cytosolic access. iPSDM lacking peroxisomes were permissive to Mtb wild-type (WT) replication but were able to restrict an Mtb mutant missing functional ESX-1, suggesting a role for peroxisomes in the control of cytosolic but not phagosomal Mtb. Using genetically encoded localization-dependent ROS probes, we found peroxisomes increased ROS levels during Mtb WT infection. Thus, human macrophages respond to the infection by increasing peroxisomes that generate ROS primarily to restrict cytosolic Mtb. Our data uncover a peroxisome-controlled, ROS-mediated mechanism that contributes to the restriction of cytosolic bacteria.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Especies Reactivas de Oxígeno
/
Peroxisomas
/
Macrófagos
/
Mycobacterium tuberculosis
Límite:
Humans
Idioma:
En
Revista:
J Cell Biol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Reino Unido