Organellar homeostasis and innate immune sensing.
Nat Rev Immunol
; 22(9): 535-549, 2022 09.
Article
en En
| MEDLINE
| ID: mdl-35197578
ABSTRACT
A cell is delimited by numerous borders that define specific organelles. The walls of some organelles are particularly robust, such as in mitochondria or endoplasmic reticulum, but some are more fluid such as in phase-separated stress granules. Either way, all organelles can be damaged at times, leading their contents to leak out into the surrounding environment. Therefore, an elegant way to construct an innate immune defence system is to recognize host molecules that do not normally reside within a particular compartment. Here, we provide several examples where organellar homeostasis is lost, leading to the activation of a specific innate immune sensor; these include NLRP3 activation owing to a disrupted trans-Golgi network, Pyrin activation due to cytoskeletal damage, and cGAS-STING activation following the leakage of nuclear or mitochondrial DNA. Frequently, organelle damage is observed downstream of pathogenic infection but it can also occur in sterile settings as associated with auto-inflammatory disease. Therefore, understanding organellar homeostasis is central to efforts that will identify new innate immune pathways, and therapeutics that balance organellar homeostasis, or target the breakdown pathways that trigger innate immune sensors, could be useful treatments for infection and chronic inflammatory diseases.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Mitocondrias
/
Nucleotidiltransferasas
Límite:
Humans
Idioma:
En
Revista:
Nat Rev Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Australia