Recruitment of hepatic macrophages from monocytes is independent of IL‐4Rα but is associated with ablation of resident macrophages in schistosomiasis.

Autor: Rolot, Marion, M. Dougall, Annette, Javaux, Justine, Lallemand, François, Machiels, Bénédicte, Martinive, Philippe, Gillet, Laurent, Dewals, Benjamin G.
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Zdroj: European Journal of Immunology; Jul2019, Vol. 49 Issue 7, p1067-1081, 15p
Abstrakt: Alternatively activated Mφs (AAMφ) accumulate in hepatic granulomas during schistosomiasis and have been suggested to originate in the bone marrow. What is less understood is how these Mφ responses are regulated after S. mansoni infection. Here, we investigated the role of IL‐4 receptor α‐chain (IL‐4Rα)‐signalling in the dynamics of liver Mφ responses. We observed that IL‐4Rα signalling was dispensable for the recruitment of Ly6Chi monocytes and for their conversion into F4/80hiCD64hiCD11bhiMφ. Moreover, while IL‐4Rα provided an AAMφ phenotype to liver F4/80hiCD64hiCD11bhiMφ that was associated with regulation of granuloma formation, it was dispensable for host survival. Resident F4/80hiCD64hiCD11bloMφ did not upregulate the AAMφ signature gene Ym1. Rather, resident Mφ nearly disappeared by week 8 after infection and artificial ablation of resident Mφ in CD169DTR mice did not affect the response to S. mansoni infection. Interestingly, ablation of CD169+ cells in naive mice resulted in the accumulation of F4/80hiCD64hiCD11bhiMφ, which was amplified when ablation occurred during schistosomiasis. Altogether, our results suggest the ablation of resident KCs after S. mansoni infection to be associated with the recruitment and accumulation of F4/80hiCD64hiCD11bhiMφ with lyz2‐dependent IL‐4Rα contributing to the regulation of granuloma inflammation but being dispensable for host survival. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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