IL-4Rα-independent expression of mannose receptor and Ym1 by macrophages depends on their IL-10 responsiveness

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dc.contributor.authorDewals, Benjamin Gen_ZA
dc.contributor.authorMarillier, Reece Gen_ZA
dc.contributor.authorHoving, Jennifer Cen_ZA
dc.contributor.authorLeeto, Mosiuoaen_ZA
dc.contributor.authorSchwegmann, Anitaen_ZA
dc.contributor.authorBrombacher, Franken_ZA
dc.date.accessioned2016-01-11T06:54:36Z
dc.date.available2016-01-11T06:54:36Z
dc.date.issued2010en_ZA
dc.description.abstractIL-4Rα-dependent responses are essential for granuloma formation and host survival during acute schistosomiasis. Previously, we demonstrated that mice deficient for macrophage-specific IL-4Rα (LysMcreIl4ra−/lox) developed increased hepatotoxicity and gut inflammation; whereas inflammation was restricted to the liver of mice lacking T cell-specific IL-4Rα expression (iLckcreIl4ra−/lox). In the study presented here we further investigated their role in liver granulomatous inflammation. Frequencies and numbers of macrophage, lymphocyte or granulocyte populations, as well as Th1/Th2 cytokine responses were similar in Schistosoma mansoni-infected LysMcreIl4ra−/lox liver granulomas, when compared to Il4ra−/lox control mice. In contrast, a shift to Th1 responses with high IFN-γ and low IL-4, IL-10 and IL-13 was observed in the severely disrupted granulomas of iLckcreIl4ra−/lox and Il4ra−/− mice. As expected, alternative macrophage activation was reduced in both LysMcreIl4ra−/lox and iLckcreIl4ra−/lox granulomas with low arginase 1 and heightened nitric oxide synthase RNA expression in granuloma macrophages of both mouse strains. Interestingly, a discrete subpopulation of SSChighCD11b+I-A/I-EhighCD204+ macrophages retained expression of mannose receptor (MMR) and Ym1 in LysMcreIl4ra−/lox but not in iLckcreIl4ra−/lox granulomas. While aaMφ were in close proximity to the parasite eggs in Il4ra−/lox control mice, MMR+Ym1+ macrophages in LysMcreIl4ra−/lox mice were restricted to the periphery of the granuloma, indicating that they might have different functions. In vivo IL-10 neutralisation resulted in the disappearance of MMR+Ym1+ macrophages in LysMcreIl4ra−/lox mice. Together, these results show that IL-4Rα-responsive T cells are essential to drive alternative macrophage activation and to control granulomatous inflammation in the liver. The data further suggest that in the absence of macrophage-specific IL-4Rα signalling, IL-10 is able to drive mannose receptor- and Ym1-positive macrophages, associated with control of hepatic granulomatous inflammation.en_ZA
dc.identifier.apacitationDewals, B. G., Marillier, R. G., Hoving, J. C., Leeto, M., Schwegmann, A., & Brombacher, F. (2010). IL-4Rα-independent expression of mannose receptor and Ym1 by macrophages depends on their IL-10 responsiveness. <i>PLOS Neglected Tropical Diseases</i>, http://hdl.handle.net/11427/16289en_ZA
dc.identifier.chicagocitationDewals, Benjamin G, Reece G Marillier, Jennifer C Hoving, Mosiuoa Leeto, Anita Schwegmann, and Frank Brombacher "IL-4Rα-independent expression of mannose receptor and Ym1 by macrophages depends on their IL-10 responsiveness." <i>PLOS Neglected Tropical Diseases</i> (2010) http://hdl.handle.net/11427/16289en_ZA
dc.identifier.citationDewals, B. G., Marillier, R. G., Hoving, J. C., Leeto, M., Schwegmann, A., & Brombacher, F. (2010). IL-4Ralpha-independent expression of mannose receptor and Ym1 by macrophages depends on their IL-10 responsiveness. PLoS Negl Trop Dis, 4(5), e689. doi:10.1371/journal.pntd.0000689en_ZA
dc.identifier.ris TY - Journal Article AU - Dewals, Benjamin G AU - Marillier, Reece G AU - Hoving, Jennifer C AU - Leeto, Mosiuoa AU - Schwegmann, Anita AU - Brombacher, Frank AB - IL-4Rα-dependent responses are essential for granuloma formation and host survival during acute schistosomiasis. Previously, we demonstrated that mice deficient for macrophage-specific IL-4Rα (LysMcreIl4ra−/lox) developed increased hepatotoxicity and gut inflammation; whereas inflammation was restricted to the liver of mice lacking T cell-specific IL-4Rα expression (iLckcreIl4ra−/lox). In the study presented here we further investigated their role in liver granulomatous inflammation. Frequencies and numbers of macrophage, lymphocyte or granulocyte populations, as well as Th1/Th2 cytokine responses were similar in Schistosoma mansoni-infected LysMcreIl4ra−/lox liver granulomas, when compared to Il4ra−/lox control mice. In contrast, a shift to Th1 responses with high IFN-γ and low IL-4, IL-10 and IL-13 was observed in the severely disrupted granulomas of iLckcreIl4ra−/lox and Il4ra−/− mice. As expected, alternative macrophage activation was reduced in both LysMcreIl4ra−/lox and iLckcreIl4ra−/lox granulomas with low arginase 1 and heightened nitric oxide synthase RNA expression in granuloma macrophages of both mouse strains. Interestingly, a discrete subpopulation of SSChighCD11b+I-A/I-EhighCD204+ macrophages retained expression of mannose receptor (MMR) and Ym1 in LysMcreIl4ra−/lox but not in iLckcreIl4ra−/lox granulomas. While aaMφ were in close proximity to the parasite eggs in Il4ra−/lox control mice, MMR+Ym1+ macrophages in LysMcreIl4ra−/lox mice were restricted to the periphery of the granuloma, indicating that they might have different functions. In vivo IL-10 neutralisation resulted in the disappearance of MMR+Ym1+ macrophages in LysMcreIl4ra−/lox mice. Together, these results show that IL-4Rα-responsive T cells are essential to drive alternative macrophage activation and to control granulomatous inflammation in the liver. The data further suggest that in the absence of macrophage-specific IL-4Rα signalling, IL-10 is able to drive mannose receptor- and Ym1-positive macrophages, associated with control of hepatic granulomatous inflammation. DA - 2010 DB - OpenUCT DO - 10.1371/journal.pntd.0000689 DP - University of Cape Town J1 - PLOS Neglected Tropical Diseases LK - https://open.uct.ac.za PB - University of Cape Town PY - 2010 T1 - IL-4Rα-independent expression of mannose receptor and Ym1 by macrophages depends on their IL-10 responsiveness TI - IL-4Rα-independent expression of mannose receptor and Ym1 by macrophages depends on their IL-10 responsiveness UR - http://hdl.handle.net/11427/16289 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16289
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pntd.0000689
dc.identifier.vancouvercitationDewals BG, Marillier RG, Hoving JC, Leeto M, Schwegmann A, Brombacher F. IL-4Rα-independent expression of mannose receptor and Ym1 by macrophages depends on their IL-10 responsiveness. PLOS Neglected Tropical Diseases. 2010; http://hdl.handle.net/11427/16289.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Immunologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2010 Dewals et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLOS Neglected Tropical Diseasesen_ZA
dc.source.urihttp://journals.plos.org/plosntdsen_ZA
dc.subject.otherMacrophagesen_ZA
dc.subject.otherGranulomasen_ZA
dc.subject.otherCytokinesen_ZA
dc.subject.otherSchistosoma mansonien_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherAnimal signaling and communicationen_ZA
dc.subject.otherFlow cytometryen_ZA
dc.subject.otherInflammationen_ZA
dc.titleIL-4Rα-independent expression of mannose receptor and Ym1 by macrophages depends on their IL-10 responsivenessen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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