Incomplete Deletion of IL-4Rα by LysM Reveals Distinct Subsets of M2 Macrophages Controlling Inflammation and Fibrosis in Chronic Schistosomiasis

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Chronic injury and inflammation lead to irreversible fibrosis in a range of diseases and infections. Macrophages alternatively activated by the immune system are capable of regulating inflammation and fibrosis, but our understanding of the source and function of these cells is incomplete. Mice genetically engineered to specifically prevent macrophages from becoming alternatively activated have been used to study the cells' role following infection with the parasite, Schistosoma mansoni. To our surprise, we found these mice prevent alternative activation only in macrophages that have had time to mature and some, perhaps more nascent, macrophages can become alternatively activated following exposure to S. mansoni eggs. We detected lower expression of Lyz2 gene in these cells, leading to less expression of the enzyme excising the receptor gene necessary for alternative activation. Following S. mansoni infection, the livers of these mice have similar levels of fibrosis but significantly more inflammation compared to controls. We conclude that during schistosomiasis, distinct populations of alternatively activated macrophages control inflammation and fibrosis: macrophages expressing low levels of Lyz2 express Arg1 and thus are sufficient to control fibrosis, while more mature Lyz2-expressing macrophages are required for downmodulation of egg-induced inflammation in chronic schistosomiasis.

Vyšlo v časopise: Incomplete Deletion of IL-4Rα by LysM Reveals Distinct Subsets of M2 Macrophages Controlling Inflammation and Fibrosis in Chronic Schistosomiasis. PLoS Pathog 10(9): e32767. doi:10.1371/journal.ppat.1004372
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004372

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