Eosinophils, but Not Type 2 Innate Lymphoid Cells, Are the Predominant Source of Interleukin 4 during the Innate Phase of Leishmania major Infection

dc.contributor.authorSasse, Carolin
dc.contributor.authorBarinberg, David
dc.contributor.authorObermeyer, Stephanie
dc.contributor.authorDebus, Andrea
dc.contributor.authorSchleicher, Ulrike
dc.contributor.authorBogdan, Christian
dc.date.accessioned2022-08-05
dc.date.available2023-10-09T20:07:16Z
dc.date.created2022
dc.date.issued2022-08-05
dc.description.abstractInterleukin (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.en
dc.identifier.citationPathogens 11.8 (2022): 828. <https://www.mdpi.com/2076-0817/11/8/828>
dc.identifier.doihttps://doi.org/10.3390/pathogens11080828
dc.identifier.issn2076-0817
dc.identifier.opus-id19969
dc.identifier.urihttps://open.fau.de/handle/openfau/19969
dc.identifier.urnurn:nbn:de:bvb:29-opus4-199691
dc.language.isoen
dc.publisherMDPI
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.de
dc.subjecteosinophils
dc.subjectinterleukin-4
dc.subjectinnate lymphoid cells (ILC)
dc.subjectILC2
dc.subjectleishmaniasis
dc.subjecttype 2 immune response
dc.subject.ddcDDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit
dc.titleEosinophils, but Not Type 2 Innate Lymphoid Cells, Are the Predominant Source of Interleukin 4 during the Innate Phase of Leishmania major Infectionen
dc.typearticle
dcterms.publisherFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
local.date.prevpublished2022-07-25
local.document.articlenumber828
local.journal.issue8
local.journal.titlePathogens
local.journal.volume11
local.sendToDnbfree*
local.subject.fakultaetMedizinische Fakultät
local.subject.importimport
local.subject.sammlungUniversität Erlangen-Nürnberg / Eingespielte Open Access Artikel / Eingespielte Open Access Artikel 2022
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