Dermis resident macrophages orchestrate localized ILC2 eosinophil circuitries to promote non-healing cutaneous leishmaniasis

Tissue-resident macrophages are critical for tissue homeostasis and repair. We previously showed that dermis-resident macrophages produce CCL24 which mediates their interaction with IL-4(+) eosinophils, required to maintain their M2-like properties in the T(H)1 environment of the Leishmania major in...

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Detalles Bibliográficos
Autores principales: Lee, Sang Hun, Kang, Byunghyun, Kamenyeva, Olena, Ferreira, Tiago Rodrigues, Cho, Kyoungin, Khillan, Jaspal S., Kabat, Juraj, Kelsall, Brian L., Sacks, David L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687111/
https://www.ncbi.nlm.nih.gov/pubmed/38030609
http://dx.doi.org/10.1038/s41467-023-43588-2
Descripción
Sumario:Tissue-resident macrophages are critical for tissue homeostasis and repair. We previously showed that dermis-resident macrophages produce CCL24 which mediates their interaction with IL-4(+) eosinophils, required to maintain their M2-like properties in the T(H)1 environment of the Leishmania major infected skin. Here, we show that thymic stromal lymphopoietin (TSLP) and IL-5(+) type 2 innate lymphoid cells are also required to maintain dermis-resident macrophages and promote infection. Single cell RNA sequencing reveals the dermis-resident macrophages as the sole source of TSLP and CCL24. Generation of Ccl24-cre mice permits specific labeling of dermis-resident macrophages and interstitial macrophages from other organs. Selective ablation of TSLP in dermis-resident macrophages reduces the numbers of IL-5(+) type 2 innate lymphoid cells, eosinophils and dermis-resident macrophages, and ameliorates infection. Our findings demonstrate that dermis-resident macrophages are self-maintained as a replicative niche for L. major by orchestrating localized type 2 circuitries with type 2 innate lymphoid cells and eosinophils.