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Tight tissue associations
The intracellular pathogen Leishmania major has been found to replicate in dermal tissue-resident macrophages (TRMs) that have an M2-like phenotype, but L. major also promotes a strong TH1 immune environment. Here, Lee et al. show that dermal TRMs can maintain an M2 phenotype in this TH1 environment through IL-4/CCL24–mediated interactions with eosinophils. Eosinophils were identified as the main source of IL-4 that drove local proliferation of dermal TRMs with M2 properties. IL-4 and IL-10 stimulation of dermal TRMs triggered production of CCL24, which promoted further eosinophil recruitment and close interactions with TRMs. These observations provide insight into this intercellular interaction that may have relevance to other inflammatory conditions.
Abstract
Tissue-resident macrophages (TRMs) maintain tissue homeostasis, but they can also provide a replicative niche for intracellular pathogens such as Leishmania. How dermal TRMs proliferate and maintain their M2 properties even in the strong TH1 environment of the L. major infected dermis is not clear. Here, we show that, in infected mice lacking IL-4/13 from eosinophils, dermal TRMs shifted to a proinflammatory state, their numbers declined, and disease was attenuated. Intravital microscopy revealed a rapid infiltration of eosinophils followed by their tight interaction with dermal TRMs. IL-4–stimulated dermal TRMs, in concert with IL-10, produced a large amount of CCL24, which functioned to amplify eosinophil influx and their interaction with dermal TRMs. An intraperitoneal helminth infection model also demonstrated a requirement for eosinophil-derived IL-4 to maintain tissue macrophages through a CCL24-mediated amplification loop. CCL24 secretion was confined to resident macrophages in other tissues, implicating eosinophil-TRM cooperative interactions in diverse inflammatory settings.
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