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Modulates the Unfolded Protein Response in during Infection
In the model organism Caenorhabditis elegans, the IRE1–XBP1 pathway, a major branch of the unfolded protein response (UPR), is required for host defense against pathogens. However, how innate immune responses activate the UPR is not fully understood. In this report, we find that Pseudomonas aeruginosa PA14 infection up-regulates the expression of the microRNA mir-233 in C. elegans. The response of mir-233 to P. aeruginosa PA14 infection is dependent on a major pathway of innate immunity, the p38 MAPK signaling cascade. The up-regulation of mir-233 is functionally important since a mutation in mir-233 leads to hypersensitivity of the nematode to the killing by P. aeruginosa PA14. Furthermore, we demonstrate that mir-233 contributes to the activation of the UPR by repressing the protein levels of its target SCA-1, a C. elegans homologue of the sarco/endoplasmic reticulum Ca2+-ATPase. Thus, mir-233 is an important regulator of the UPR during the innate immune response.
Vyšlo v časopise: Modulates the Unfolded Protein Response in during Infection. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004606
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004606Souhrn
In the model organism Caenorhabditis elegans, the IRE1–XBP1 pathway, a major branch of the unfolded protein response (UPR), is required for host defense against pathogens. However, how innate immune responses activate the UPR is not fully understood. In this report, we find that Pseudomonas aeruginosa PA14 infection up-regulates the expression of the microRNA mir-233 in C. elegans. The response of mir-233 to P. aeruginosa PA14 infection is dependent on a major pathway of innate immunity, the p38 MAPK signaling cascade. The up-regulation of mir-233 is functionally important since a mutation in mir-233 leads to hypersensitivity of the nematode to the killing by P. aeruginosa PA14. Furthermore, we demonstrate that mir-233 contributes to the activation of the UPR by repressing the protein levels of its target SCA-1, a C. elegans homologue of the sarco/endoplasmic reticulum Ca2+-ATPase. Thus, mir-233 is an important regulator of the UPR during the innate immune response.
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