M2-like, dermal macrophages are maintained via IL-4/CCL24–mediated cooperative interaction with eosinophils in cutaneous leishmaniasis
- 10 April 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Immunology
- Vol. 5 (46)
- https://doi.org/10.1126/sciimmunol.aaz4415
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.Keywords
Funding Information
- National Institute of Allergy and Infectious Diseases
This publication has 52 references indexed in Scilit:
- Local Macrophage Proliferation, Rather than Recruitment from the Blood, Is a Signature of T H 2 InflammationScience, 2011
- Eosinophils Sustain Adipose Alternatively Activated Macrophages Associated with Glucose HomeostasisScience, 2011
- How are TH2-type immune responses initiated and amplified?Nature Reviews Immunology, 2010
- Eosinophils and Th2 immunity: contemporary insightsImmunology & Cell Biology, 2010
- Efficient generation of long-distance conditional alleles using recombineering and a dual selection strategy in replicate platesBMC Biotechnology, 2009
- iNOS-Producing Inflammatory Dendritic Cells Constitute the Major Infected Cell Type during the Chronic Leishmania major Infection Phase of C57BL/6 Resistant MicePLoS Pathogens, 2009
- The Immunological Genome Project: networks of gene expression in immune cellsNature Immunology, 2008
- Tissue expression of inducible nitric oxide synthase is closely associated with resistance to Leishmania major.The Journal of Experimental Medicine, 1994
- Macrophages secrete a novel heparin-binding protein with inflammatory and neutrophil chemokinetic properties.The Journal of Experimental Medicine, 1988
- Eosinophilia, mast cell hyperplasia and antibody production in rats following an intraperitoneal injection of ascaris cuticle including in-vitro studies of immune eosinophil granule lysisPathology, 1985