Caveolin-1 controls vesicular TLR2 expression, p38 signaling and T cell suppression in BCG infected Murine Monocytic myeloid-derived suppressor cells

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dc.contributor.authorJohn, Vinien_ZA
dc.contributor.authorKotze, Leigh A.en_ZA
dc.contributor.authorRibechini, Elianaen_ZA
dc.contributor.authorWalzl, Gerharden_ZA
dc.contributor.authorDu Plessis, Nelitaen_ZA
dc.contributor.authorLutz, Manfred B.en_ZA
dc.date.accessioned2021-09-17T08:52:43Zen_ZA
dc.date.available2021-09-17T08:52:43Zen_ZA
dc.date.issued2019en_ZA
dc.descriptionCITATION: John V, et al. 2019. Caveolin-1 controls vesicular TLR2 expression, p38 signaling and T cell suppression in BCG infected Murine Monocytic myeloid-derived suppressor cells. Frontiers in Immunology, 10. doi:10.3389/fimmu.2019.02826en_ZA
dc.descriptionThe original publication is available at https://www.frontiersin.org/journals/immunologyen_ZA
dc.description.abstractMonocytic myeloid-derived suppressor cells (M-MDSCs) and granulocytic MDSCs (G-MDSCs) have been found to be massively induced in TB patients as well in murine Mtb infection models. However, the interaction of mycobacteria with MDSCs and its role in TB infection is not well studied. Here, we investigated the role of Cav-1 for MDSCs infected with Mycobacterium bovis Bacille-Calmette-Guerín (BCG). MDSCs that were generated from murine bone marrow (MDSCs) of wild-type (WT) or Cav1−/− mice upregulated Cav-1, TLR4 and TLR2 expression after BCG infection on the cell surface. However, Cav-1 deficiency resulted in a selective defect of intracellular TLR2 levels predominantly in the M-MDSC subset. Further analysis indicated no difference in the phagocytosis of BCG by M-MDSCs from WT and Cav1−/− mice or caveosome formation, but a reduced capacity to up-regulate surface markers, to secrete various cytokines, to induce iNOS and NO production required for suppression of T cell proliferation, whereas Arg-1 was not affected. Among the signaling pathways affected by Cav-1 deficiency, we found lower phosphorylation of the p38 mitogen-activated protein kinase (MAPK). Together, our findings implicate that (i) Cav-1 is dispensable for the internalization of BCG, (ii) vesicular TLR2 signaling in M-MDSCs is a major signaling pathway induced by BCG, (iii) vesicular TLR2 signals are controlled by Cav-1, (iv) vesicular TLR2/Cav-1 signaling is required for T cell suppressor functions.en_ZA
dc.description.urihttps://www.frontiersin.org/articles/10.3389/fimmu.2019.02826/fullen_ZA
dc.description.versionPublisher's versionen_ZA
dc.format.extent15 pagesen_ZA
dc.identifier.citationJohn V, et al. 2019. Caveolin-1 controls vesicular TLR2 expression, p38 signaling and T cell suppression in BCG infected Murine Monocytic myeloid-derived suppressor cells. Frontiers in Immunology, 10. doi:10.3389/fimmu.2019.02826en_ZA
dc.identifier.issn1664-3224 (online)en_ZA
dc.identifier.otherdoi:10.3389/fimmu.2019.02826en_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/123042en_ZA
dc.language.isoen_ZAen_ZA
dc.publisherFrontiers Mediaen_ZA
dc.rights.holderAuthors retain rightsen_ZA
dc.subjectTuberculosis -- Patientsen_ZA
dc.subjectIntracellular pathogensen_ZA
dc.subjectMyeloid-derived suppressor cell (MDSC)en_ZA
dc.subjectMycobacterium tuberculosisen_ZA
dc.subjectCaveolin-1 (Cav-1)en_ZA
dc.subjectT cell suppressionen_ZA
dc.titleCaveolin-1 controls vesicular TLR2 expression, p38 signaling and T cell suppression in BCG infected Murine Monocytic myeloid-derived suppressor cellsen_ZA
dc.typeArticleen_ZA
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