%0 Journal Article
%T IL-4R¦Á-Independent Expression of Mannose Receptor and Ym1 by Macrophages Depends on their IL-10 Responsiveness
%A Benjamin G. Dewals
%A Reece G. Marillier
%A Jennifer C. Hoving
%A Mosiuoa Leeto
%A Anita Schwegmann
%A Frank Brombacher
%J PLOS Neglected Tropical Diseases
%D 2010
%I Public Library of Science (PLoS)
%R 10.1371/journal.pntd.0000689
%X IL-4R¦Á-dependent responses are essential for granuloma formation and host survival during acute schistosomiasis. Previously, we demonstrated that mice deficient for macrophage-specific IL-4R¦Á (LysMcreIl4ra£¿/lox) developed increased hepatotoxicity and gut inflammation; whereas inflammation was restricted to the liver of mice lacking T cell-specific IL-4R¦Á 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-¦Ã 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 aaM¦Õ 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-4R¦Á-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-4R¦Á signalling, IL-10 is able to drive mannose receptor- and Ym1-positive macrophages, associated with control of hepatic granulomatous inflammation.
%U http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0000689