M2-like, dermal macrophages are maintained via IL-4/CCL24–mediated cooperative interaction with eosinophils in cutaneous leishmaniasis

• DOI: 10.1126/sciimmunol.aaz4415
• Publication Date: 2020-04-10T23:16:59Z
• Authors: Sang Hun Lee; Mariana M. Chaves; Olena Kamenyeva; Pedro H. Gazzinel...; Byunghyun Kang; Gabriela Pessenda; Katiuska Passelli; Fabienne Tacchini...; Juraj Kabat; Elizabeth A. Jaco...; Thomas B. Nutman; David L. Sacks
• Keywords: Infiltration (HVAC); Proinflammatory cytokine

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 their M2 properties even in the strong TH1 environment of L. major infected dermis is not clear. Here, we show that, mice lacking IL-4/13 from eosinophils, shifted to proinflammatory state, numbers declined, disease was attenuated. Intravital microscopy revealed rapid infiltration eosinophils followed by tight interaction with TRMs. IL-4-stimulated TRMs, concert IL-10, produced large amount CCL24, which functioned amplify eosinophil influx An intraperitoneal helminth infection model demonstrated requirement eosinophil-derived IL-4 through CCL24-mediated amplification loop. CCL24 secretion confined resident other tissues, implicating eosinophil-TRM cooperative interactions diverse inflammatory settings.