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- Title
Distinct Roles for IL-1 Receptor Type I Signaling in Early Versus Established Leishmania major Infections.
- Authors
Kostka, Susanna Lopez; Knop, Jürgen; Konur, Abdo; Udey, Mark C.; von Stebut, Esther
- Abstract
IL-1α/β released by infected dendritic cells (DC) plays a critical role in the development of protective immunity against Leishmania major. Previous studies demonstrated that treatment of susceptible BALB/c mice with IL-1α during T-cell priming (days 1–3 post-infection) induced T helper (Th)1-mediated protection. In contrast, we now demonstrate that prolonged treatment with IL-1α (for 3 weeks) worsened disease outcome. To characterize the receptor involved, L. major infections in IL-1 receptor type I (IL-1RI) knockout mice were studied. In C57BL/6 IL-1RI−/− mice, the IL-1α-mediated protective effect was abrogated. The course of high-dose infection (2 × 105 parasites) in IL-1RI−/− mice was not different from controls. Surprisingly, in low-dose infections (103 parasites), IL-1RI−/− mice developed ∼50% smaller lesions compared to wild types, decreased parasite loads and increased IFNγ/IL-4 ratios. Interestingly, naive Th0 and Th2, but not Th1, cells expressed IL-1RI ex vivo. We conclude that IL-1RI mediates the effect of IL-1α in leishmaniasis in C57BL/6 mice. In addition, IL-1 appears to play distinct roles in Th education and maintenance. In early phases of physiologically relevant, low-dose L. major infections, IL-1 facilitates Th1 development from Th0 cells, whereas later on IL-1RI signaling promotes Th2 expansion and worsens disease outcome. Effects of IL-1 on disease outcome may be related to levels of IL-1RI on Th subpopulations.Journal of Investigative Dermatology (2006) 126, 1582–1589. doi:10.1038/sj.jid.5700309; published online 27 April 2006
- Subjects
DENDRITIC cells; INTERLEUKIN-1; CUTANEOUS leishmaniasis; T cells; DERMATOLOGY
- Publication
Journal of Investigative Dermatology, 2006, Vol 126, Issue 7, p1582
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1038/sj.jid.5700309