ß-Barrel outer membrane proteins suppress mTORC2 activation and induce autophagic responses.
Sci Signal
; 11(558)2018 11 27.
Article
in En
| MEDLINE
| ID: mdl-30482849
ABSTRACT
The outer membranes of Gram-negative bacteria and mitochondria contain proteins with a distinct ß-barrel tertiary structure that could function as a molecular pattern recognized by the innate immune system. Here, we report that purified outer membrane proteins (OMPs) from different bacterial and mitochondrial sources triggered the induction of autophagy-related endosomal acidification, LC3B lipidation, and p62 degradation. Furthermore, OMPs reduced the phosphorylation and therefore activation of the multiprotein complex mTORC2 and its substrate Akt in macrophages and epithelial cells. The cell surface receptor SlamF8 and the DNA-protein kinase subunit XRCC6 were required for these OMP-specific responses in macrophages and epithelial cells, respectively. The addition of OMPs to mouse bone marrow-derived macrophages infected with Salmonella Typhimurium facilitated bacterial clearance. These data identify a specific cellular response mediated by bacterial and mitochondrial OMPs that can alter inflammatory responses and influence the killing of pathogens.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Salmonella Infections
/
Autophagy
/
Bacterial Outer Membrane Proteins
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Monocytes
/
Cell Membrane
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Mitochondrial Membranes
/
Mechanistic Target of Rapamycin Complex 2
Limits:
Animals
/
Humans
Language:
En
Journal:
Sci Signal
Journal subject:
CIENCIA
/
FISIOLOGIA
Year:
2018
Document type:
Article
Affiliation country:
United States