scholarly journals A new paradigm: innate immune sensing of viruses via the unfolded protein response

2014 ◽  
Vol 5 ◽  
Author(s):  
Judith A. Smith
Keyword(s):  
Unfolded Protein Response ◽  
Innate Immune ◽  
New Paradigm ◽  
Unfolded Protein ◽  
Immune Sensing ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Innate Immune Sensing

scholarly journals Inhibition of host cell translation elongation byLegionella pneumophilablocks the host cell unfolded protein response

2015 ◽  
Vol 112 (49) ◽  
pp. E6790-E6797 ◽  
Author(s):  
Andrew D. Hempstead ◽  
Ralph R. Isberg
Keyword(s):  
Host Cell ◽  
Unfolded Protein Response ◽  
Legionella Pneumophila ◽  
Protein Translation ◽  
Innate Immune ◽  
Host Protein ◽  
Translation Elongation ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

Cells of the innate immune system recognize bacterial pathogens by detecting common microbial patterns as well as pathogen-specific activities. One system that responds to these stimuli is the IRE1 branch of the unfolded protein response (UPR), a sensor of endoplasmic reticulum (ER) stress. Activation of IRE1, in the context of Toll-like receptor (TLR) signaling, induces strong proinflammatory cytokine induction. We show here thatLegionella pneumophila, an intravacuolar pathogen that replicates in an ER-associated compartment, blocks activation of the IRE1 pathway despite presenting pathogen products that stimulate this response.L. pneumophilaTLR ligands induced the splicing of mRNA encoding XBP1s, the main target of IRE1 activity.L. pneumophilawas able to inhibit both chemical and bacterial induction of XBP1 splicing via bacterial translocated proteins that interfere with host protein translation. A strain lacking five translocated translation elongation inhibitors was unable to block XBP1 splicing, but this could be rescued by expression of a single such inhibitor, consistent with limitation of the response by translation elongation inhibitors. Chemical inhibition of translation elongation blocked pattern recognition receptor-mediated XBP1 splicing, mimicking the effects of the bacterial translation inhibitors. In contrast, host cell-promoted inhibition of translation initiation in response to the pathogen was ineffective in blocking XBP1 splicing, demonstrating the need for the elongation inhibitors for protection from the UPR. The inhibition of host translation elongation may be a common strategy used by pathogens to limit the innate immune response by interfering with signaling via the UPR.

Oestrogen-driven changes in the bovine uterus are associated with activation of the unfolded protein response

2014 ◽  
Author(s):  
Mohammed A Alfattah ◽  
Paul Anthony McGettigan ◽  
John Arthur Browne ◽  
Khalid M Alkhodair ◽  
Katarzyna Pluta ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response
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