{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T11:09:37Z","timestamp":1793185777350,"version":"4.5.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Autophagy plays an important role in recognizing and protecting cells from invading intracellular pathogens such as <jats:italic>Salmonella<\/jats:italic>. In this work, we investigated the role of p38<jats:sup>MAPK<\/jats:sup>\/MK2 in modulating the host cell susceptibility to <jats:italic>Salmonella<\/jats:italic> infection. Inhibition of p38<jats:sup>MAPK<\/jats:sup> or MK2 led to a significant increase of bacterial counts in <jats:italic>Salmonella<\/jats:italic> infected mouse embryonic fibroblasts (MEFs), as well as in MK2-deficient (<jats:italic>Mk2<jats:sup>-\/-<\/jats:sup><\/jats:italic>) cells. Furthermore, western blot analysis showed that <jats:italic>Mk2<jats:sup>-\/-<\/jats:sup><\/jats:italic> cells have lower level of LC3 lipidation, which is the indicator of general autophagy compared to <jats:italic>Mk2<\/jats:italic>-rescued cells. In <jats:italic>Mk2<jats:sup>-\/-<\/jats:sup><\/jats:italic> cells, we also observed lower activated TANK-binding kinase-1 phosphorylation on Ser172 and p62\/SQTM1-Ser403 phosphorylation, which are important to promote the translocation of p62 to ubiquitinated microbes and required for efficient autophagy of bacteria. Furthermore, immunofluorescence analysis revealed reduced colocalization of <jats:italic>Salmonella<\/jats:italic> with LC3 and p62 in MEFs. Inhibition of autophagy with bafilomycin A1 showed increased bacterial counts in treated cells compared to control cell. Overall, these results indicate that p38<jats:sup>MAPK<\/jats:sup>\/MK2-mediated protein phosphorylation modulates the host cell susceptibility to <jats:italic>Salmonella<\/jats:italic> infection by affecting the autophagy pathways.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1245443","type":"journal-article","created":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T06:33:41Z","timestamp":1694586821000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["p38MAPK\/MK2 signaling stimulates host cells autophagy pathways to restrict Salmonella infection"],"prefix":"10.3389","volume":"14","author":[{"given":"Abdulhadi","family":"Suwandi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoj 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