RT Journal Article
T1 Reprogramming of microRNA expression via E2F1 downregulation promotes Salmonella infection both in infected and bystander cells
A1 Aguilar, Carmen
A1 Costa, Susana
A1 Maudet, Claire
A1 Vivek-Ananth, R.P.
A1 Zaldívar-López, Sara
A1 Garrido, Juan J.
A1 Samal, Areejit
A1 Mano, Miguel
A1 Eulalio, Ana
K1 Bacterial pathogenesis
K1 Cellular microbiology
K1 Pathogens
K1 MiRNAs
K1 Salmonella Infections
K1 Salmonella
K1 Patógenos
K1 MicroARNs
K1 Infecciones por Salmonella
AB Cells infected with pathogens can contribute to clearing infections by releasing signals that instruct neighbouring cells to mount a pro-inflammatory cytokine response, or by other mechanisms that reduce bystander cells' susceptibility to infection. Here, we show the opposite effect: epithelial cells infected with Salmonella Typhimurium secrete host factors that facilitate the infection of bystander cells. We find that the endoplasmic reticulum stress response is activated in both infected and bystander cells, and this leads to activation of JNK pathway, downregulation of transcription factor E2F1, and consequent reprogramming of microRNA expression in a time-dependent manner. These changes are not elicited by infection with other bacterial pathogens, such as Shigella flexneri or Listeria monocytogenes. Remarkably, the protein HMGB1 present in the secretome of Salmonella-infected cells is responsible for the activation of the IRE1 branch of the endoplasmic reticulum stress response in non-infected, neighbouring cells. Furthermore, E2F1 downregulation and the associated microRNA alterations promote Salmonella replication within infected cells and prime bystander cells for more efficient infection.
PB Springer Nature
YR 2021
FD 2021-06-07
LK http://hdl.handle.net/10668/3741
UL http://hdl.handle.net/10668/3741
LA en
NO Aguilar C, Costa S, Maudet C, Vivek-Ananth RP, Zaldívar-López S, Garrido JJ, et al. Reprogramming of microRNA expression via E2F1 downregulation promotes Salmonella infection both in infected and bystander cells. Nat Commun. 2021 Jun 7;12(1):3392
DS RISalud
RD Apr 19, 2025