TY - JOUR
T1 - Stress-induced host membrane remodeling protects from infection by non-motile bacterial pathogens
AU - Tawk, Caroline
AU - Nigro, Giulia
AU - Rodrigues Lopes, Ines
AU - Aguilar, Carmen
AU - Lisowski, Clivia
AU - Mano, Miguel
AU - Sansonetti, Philippe
AU - Vogel, Jörg
AU - Eulalio, Ana
N1 - Funding Information:
C.T. was a recipient of a PhD fellowship from the Graduate School of Life Sciences, University of W?rzburg. This work was supported by grants from the Bavarian Ministry of Sciences, Research and the Arts in the framework of the Bavarian Molecular Biosystems Research Network (BioSysNet to J.V and A.E.), and the European Research Council (ERC) Advanced Grant (GA no. 339579 to P.S).
Funding Information:
C.T. was a recipient of a PhD fellowship from the Graduate School of Life Sciences, University of Würzburg. This work was supported by grants from the Bavarian Ministry of Sciences, Research and the Arts in the framework of the Bavarian Molecular Biosystems Research Network (BioSysNet to J.V and A.E.), and the European Research Council (ERC) Advanced Grant (GA no. 339579 to P.S).
Publisher Copyright:
© 2018 The Authors. Published under the terms of the CC BY 4.0 license
PY - 2018/12/3
Y1 - 2018/12/3
N2 - While mucosal inflammation is a major source of stress during enteropathogen infection, it remains to be fully elucidated how the host benefits from this environment to clear the pathogen. Here, we show that host stress induced by different stimuli mimicking inflammatory conditions strongly reduces the binding of Shigella flexneri to epithelial cells. Mechanistically, stress activates acid sphingomyelinase leading to host membrane remodeling. Consequently, knockdown or pharmacological inhibition of the acid sphingomyelinase blunts the stress-dependent inhibition of Shigella binding to host cells. Interestingly, stress caused by intracellular Shigella replication also results in remodeling of the host cell membrane, in vitro and in vivo, which precludes re-infection by this and other non-motile pathogens. In contrast, Salmonella Typhimurium overcomes the shortage of permissive entry sites by gathering effectively at the remaining platforms through its flagellar motility. Overall, our findings reveal host membrane remodeling as a novel stress-responsive cell-autonomous defense mechanism that protects epithelial cells from infection by non-motile bacterial pathogens.
AB - While mucosal inflammation is a major source of stress during enteropathogen infection, it remains to be fully elucidated how the host benefits from this environment to clear the pathogen. Here, we show that host stress induced by different stimuli mimicking inflammatory conditions strongly reduces the binding of Shigella flexneri to epithelial cells. Mechanistically, stress activates acid sphingomyelinase leading to host membrane remodeling. Consequently, knockdown or pharmacological inhibition of the acid sphingomyelinase blunts the stress-dependent inhibition of Shigella binding to host cells. Interestingly, stress caused by intracellular Shigella replication also results in remodeling of the host cell membrane, in vitro and in vivo, which precludes re-infection by this and other non-motile pathogens. In contrast, Salmonella Typhimurium overcomes the shortage of permissive entry sites by gathering effectively at the remaining platforms through its flagellar motility. Overall, our findings reveal host membrane remodeling as a novel stress-responsive cell-autonomous defense mechanism that protects epithelial cells from infection by non-motile bacterial pathogens.
KW - acid sphingomyelinase
KW - host stress response
KW - membrane remodeling
KW - Salmonella
KW - Shigella
UR - http://www.scopus.com/inward/record.url?scp=85055918371&partnerID=8YFLogxK
U2 - 10.15252/embj.201798529
DO - 10.15252/embj.201798529
M3 - Article
C2 - 30389666
AN - SCOPUS:85055918371
SN - 0261-4189
VL - 37
JO - EMBO Journal
JF - EMBO Journal
IS - 23
M1 - e98529
ER -