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

Sang Hun Lee, Mariana M. Chaves, Olena Kamenyeva, Pedro H. Gazzinelli-Guimaraes, Byunghyun Kang, Gabriela Pessenda, Katiuska Passelli, Fabienne Tacchini-Cottier, Juraj Kabat, Elizabeth A. Jacobsen, Thomas B. Nutman, David L. Sacks

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbereaaz4415
JournalScience Immunology
Volume5
Issue number46
DOIs
StatePublished - 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Lee, S. H., Chaves, M. M., Kamenyeva, O., Gazzinelli-Guimaraes, P. H., Kang, B., Pessenda, G., Passelli, K., Tacchini-Cottier, F., Kabat, J., Jacobsen, E. A., Nutman, T. B., & Sacks, D. L. (2020). M2-like, dermal macrophages are maintained via IL-4/CCL24-mediated cooperative interaction with eosinophils in cutaneous leishmaniasis. Science Immunology, 5(46), [eaaz4415]. https://doi.org/10.1126/sciimmunol.aaz4415