IL-4Ralpha-independent expression of mannose receptor and Ym1 by macrophages depends on their IL-10 responsiveness.
IL-4Ralpha-dependent responses are essential for granuloma formation and host survival during acute schistosomiasis. Previously, we demonstrated that mice deficient for macrophage-specific IL-4Ralpha (LysM(cre)Il4ra(-/lox)) developed increased hepatotoxicity and gut inflammation; whereas inflammatio...
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ftdoajarticles:oai:doaj.org/article:8e61bb39d280441db13b0bc4e3f4dacd 2023-05-15T15:17:43+02:00 IL-4Ralpha-independent expression of mannose receptor and Ym1 by macrophages depends on their IL-10 responsiveness. Benjamin G Dewals Reece G Marillier Jennifer C Hoving Mosiuoa Leeto Anita Schwegmann Frank Brombacher 2010-05-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0000689 https://doaj.org/article/8e61bb39d280441db13b0bc4e3f4dacd EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC2872644?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000689 https://doaj.org/article/8e61bb39d280441db13b0bc4e3f4dacd PLoS Neglected Tropical Diseases, Vol 4, Iss 5, p e689 (2010) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2010 ftdoajarticles https://doi.org/10.1371/journal.pntd.0000689 2022-12-31T10:28:34Z IL-4Ralpha-dependent responses are essential for granuloma formation and host survival during acute schistosomiasis. Previously, we demonstrated that mice deficient for macrophage-specific IL-4Ralpha (LysM(cre)Il4ra(-/lox)) developed increased hepatotoxicity and gut inflammation; whereas inflammation was restricted to the liver of mice lacking T cell-specific IL-4Ralpha expression (iLck(cre)Il4ra(-/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 LysM(cre)Il4ra(-/lox) liver granulomas, when compared to Il4ra(-/lox) control mice. In contrast, a shift to Th1 responses with high IFN-gamma and low IL-4, IL-10 and IL-13 was observed in the severely disrupted granulomas of iLck(cre)Il4ra(-/lox) and Il4ra(-/-) mice. As expected, alternative macrophage activation was reduced in both LysM(cre)Il4ra(-/lox) and iLck(cre)Il4ra(-/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 SSC(high)CD11b+I-A/I-E(high)CD204+ macrophages retained expression of mannose receptor (MMR) and Ym1 in LysM(cre)Il4ra(-/lox) but not in iLck(cre)Il4ra(-/lox) granulomas. While aaMphi were in close proximity to the parasite eggs in Il4ra(-/lox) control mice, MMR+Ym1+ macrophages in LysM(cre)Il4ra(-/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 LysM(cre)Il4ra(-/lox) mice. Together, these results show that IL-4Ralpha-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-4Ralpha signalling, IL-10 is able to drive ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 4 5 e689 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Benjamin G Dewals Reece G Marillier Jennifer C Hoving Mosiuoa Leeto Anita Schwegmann Frank Brombacher IL-4Ralpha-independent expression of mannose receptor and Ym1 by macrophages depends on their IL-10 responsiveness. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
IL-4Ralpha-dependent responses are essential for granuloma formation and host survival during acute schistosomiasis. Previously, we demonstrated that mice deficient for macrophage-specific IL-4Ralpha (LysM(cre)Il4ra(-/lox)) developed increased hepatotoxicity and gut inflammation; whereas inflammation was restricted to the liver of mice lacking T cell-specific IL-4Ralpha expression (iLck(cre)Il4ra(-/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 LysM(cre)Il4ra(-/lox) liver granulomas, when compared to Il4ra(-/lox) control mice. In contrast, a shift to Th1 responses with high IFN-gamma and low IL-4, IL-10 and IL-13 was observed in the severely disrupted granulomas of iLck(cre)Il4ra(-/lox) and Il4ra(-/-) mice. As expected, alternative macrophage activation was reduced in both LysM(cre)Il4ra(-/lox) and iLck(cre)Il4ra(-/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 SSC(high)CD11b+I-A/I-E(high)CD204+ macrophages retained expression of mannose receptor (MMR) and Ym1 in LysM(cre)Il4ra(-/lox) but not in iLck(cre)Il4ra(-/lox) granulomas. While aaMphi were in close proximity to the parasite eggs in Il4ra(-/lox) control mice, MMR+Ym1+ macrophages in LysM(cre)Il4ra(-/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 LysM(cre)Il4ra(-/lox) mice. Together, these results show that IL-4Ralpha-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-4Ralpha signalling, IL-10 is able to drive ... |
format |
Article in Journal/Newspaper |
author |
Benjamin G Dewals Reece G Marillier Jennifer C Hoving Mosiuoa Leeto Anita Schwegmann Frank Brombacher |
author_facet |
Benjamin G Dewals Reece G Marillier Jennifer C Hoving Mosiuoa Leeto Anita Schwegmann Frank Brombacher |
author_sort |
Benjamin G Dewals |
title |
IL-4Ralpha-independent expression of mannose receptor and Ym1 by macrophages depends on their IL-10 responsiveness. |
title_short |
IL-4Ralpha-independent expression of mannose receptor and Ym1 by macrophages depends on their IL-10 responsiveness. |
title_full |
IL-4Ralpha-independent expression of mannose receptor and Ym1 by macrophages depends on their IL-10 responsiveness. |
title_fullStr |
IL-4Ralpha-independent expression of mannose receptor and Ym1 by macrophages depends on their IL-10 responsiveness. |
title_full_unstemmed |
IL-4Ralpha-independent expression of mannose receptor and Ym1 by macrophages depends on their IL-10 responsiveness. |
title_sort |
il-4ralpha-independent expression of mannose receptor and ym1 by macrophages depends on their il-10 responsiveness. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2010 |
url |
https://doi.org/10.1371/journal.pntd.0000689 https://doaj.org/article/8e61bb39d280441db13b0bc4e3f4dacd |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 4, Iss 5, p e689 (2010) |
op_relation |
http://europepmc.org/articles/PMC2872644?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000689 https://doaj.org/article/8e61bb39d280441db13b0bc4e3f4dacd |
op_doi |
https://doi.org/10.1371/journal.pntd.0000689 |
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PLoS Neglected Tropical Diseases |
container_volume |
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container_issue |
5 |
container_start_page |
e689 |
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