Abstract
Interleukin (IL)-4 plays a central role in the initiation of a type 2 T helper cell (Th2) response, which leads to non-healing and progressive infections with the protozoan parasite Leishmania (L.) major. Here, we tested the hypothesis that type 2 innate lymphoid cells (ILC2), which promote the development of Th2 cells, form an important source of IL-4 early after intradermal or subcutaneous L. major infection. Lineage-marker negative CD90.2+CD127+PD1− ILC2 were readily detectable in the ear or foot skin, but hardly in the draining lymph nodes of both naïve and L. major-infected self-healing C57BL/6 and non-healing BALB/c mice and made up approximately 20% to 30% of all CD45+SiglecF− cells. Dermal ILC2 of C57BL/6 mice expressed the inducible T cell-costimulator (ICOS, CD278), whereas BALB/C ILC2 were positive for the stem cell antigen (Sca)-1. Within the first 5 days of infection, the absolute numbers of ILC2 did not significantly change in the dermis, which is in line with the unaltered expression of cytokines activating (IL-18, IL-25, IL-33, TSLP) or inhibiting ILC2 (IL-27, IFN-γ). At day 5 to 6 post infection, we observed an upregulation of IL-4, but not of IL-5, IL-10 or IL-13 mRNA. Using IL-4-reporter (4get) mice, we found that the production of IL-4 by C57BL/6 or BALB/c mice was largely restricted to CD45+SiglecF+ cells of high granularity, i.e., eosinophils. From these data, we conclude that eosinophils, but not ILC2, are a major innate source of IL-4 at the skin site of L. major infection.
Funder
Federal Ministry of Education and Research
Interdisciplinary Center for Clinical Research (IZKF), Universitätsklinikum Erlangen
Subject
Infectious Diseases,Microbiology (medical),General Immunology and Microbiology,Molecular Biology,Immunology and Allergy
Cited by
5 articles.
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