p38MAPK/MK2 signaling stimulates host cells autophagy pathways to restrict Salmonella infection
Autophagy plays an important role in recognizing and protecting cells from invading intracellular pathogens such as Salmonella. In this work, we investigated the role of p38MAPK/MK2 in modulating the host cell susceptibility to Salmonella infection. Inhibition of p38MAPK or MK2 led to a significant...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1245443/full |
| _version_ | 1797687557747638272 |
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| author | Abdulhadi Suwandi Manoj B. Menon Alexey Kotlyarov Guntram A. Grassl Guntram A. Grassl Matthias Gaestel |
| author_facet | Abdulhadi Suwandi Manoj B. Menon Alexey Kotlyarov Guntram A. Grassl Guntram A. Grassl Matthias Gaestel |
| author_sort | Abdulhadi Suwandi |
| collection | DOAJ |
| description | Autophagy plays an important role in recognizing and protecting cells from invading intracellular pathogens such as Salmonella. In this work, we investigated the role of p38MAPK/MK2 in modulating the host cell susceptibility to Salmonella infection. Inhibition of p38MAPK or MK2 led to a significant increase of bacterial counts in Salmonella infected mouse embryonic fibroblasts (MEFs), as well as in MK2-deficient (Mk2-/-) cells. Furthermore, western blot analysis showed that Mk2-/- cells have lower level of LC3 lipidation, which is the indicator of general autophagy compared to Mk2-rescued cells. In Mk2-/- 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 Salmonella 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 p38MAPK/MK2-mediated protein phosphorylation modulates the host cell susceptibility to Salmonella infection by affecting the autophagy pathways. |
| first_indexed | 2024-03-12T01:20:33Z |
| format | Article |
| id | doaj.art-79d6627d802a45bf991f59e8a0574ba8 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T01:20:33Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-79d6627d802a45bf991f59e8a0574ba82023-09-13T06:33:17ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12454431245443p38MAPK/MK2 signaling stimulates host cells autophagy pathways to restrict Salmonella infectionAbdulhadi Suwandi0Manoj B. Menon1Alexey Kotlyarov2Guntram A. Grassl3Guntram A. Grassl4Matthias Gaestel5Institute of Cell Biochemistry, Hannover Medical School, Hannover, GermanyKusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, IndiaInstitute of Cell Biochemistry, Hannover Medical School, Hannover, GermanyInstitute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, GermanyGerman Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Hannover, GermanyInstitute of Cell Biochemistry, Hannover Medical School, Hannover, GermanyAutophagy plays an important role in recognizing and protecting cells from invading intracellular pathogens such as Salmonella. In this work, we investigated the role of p38MAPK/MK2 in modulating the host cell susceptibility to Salmonella infection. Inhibition of p38MAPK or MK2 led to a significant increase of bacterial counts in Salmonella infected mouse embryonic fibroblasts (MEFs), as well as in MK2-deficient (Mk2-/-) cells. Furthermore, western blot analysis showed that Mk2-/- cells have lower level of LC3 lipidation, which is the indicator of general autophagy compared to Mk2-rescued cells. In Mk2-/- 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 Salmonella 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 p38MAPK/MK2-mediated protein phosphorylation modulates the host cell susceptibility to Salmonella infection by affecting the autophagy pathways.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1245443/fullp38MAPKMK2cell signalingSalmonellainfectionautophagy |
| spellingShingle | Abdulhadi Suwandi Manoj B. Menon Alexey Kotlyarov Guntram A. Grassl Guntram A. Grassl Matthias Gaestel p38MAPK/MK2 signaling stimulates host cells autophagy pathways to restrict Salmonella infection Frontiers in Immunology p38MAPK MK2 cell signaling Salmonella infection autophagy |
| title | p38MAPK/MK2 signaling stimulates host cells autophagy pathways to restrict Salmonella infection |
| title_full | p38MAPK/MK2 signaling stimulates host cells autophagy pathways to restrict Salmonella infection |
| title_fullStr | p38MAPK/MK2 signaling stimulates host cells autophagy pathways to restrict Salmonella infection |
| title_full_unstemmed | p38MAPK/MK2 signaling stimulates host cells autophagy pathways to restrict Salmonella infection |
| title_short | p38MAPK/MK2 signaling stimulates host cells autophagy pathways to restrict Salmonella infection |
| title_sort | p38mapk mk2 signaling stimulates host cells autophagy pathways to restrict salmonella infection |
| topic | p38MAPK MK2 cell signaling Salmonella infection autophagy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1245443/full |
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