| Distinct roles for IL-1 receptor type I signaling in early versus established Leishmania major infections. | |
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MedLine Citation:
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PMID: 16645594 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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IL-1alpha/beta 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-1alpha 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-1alpha (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-1alpha-mediated protective effect was abrogated. The course of high-dose infection (2 x 10(5) parasites) in IL-1RI-/- mice was not different from controls. Surprisingly, in low-dose infections (10(3) parasites), IL-1RI-/- mice developed approximately 50% smaller lesions compared to wild types, decreased parasite loads and increased IFNgamma/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-1alpha 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. |
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Authors:
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Susanna Lopez Kostka; Jürgen Knop; Abdo Konur; Mark C Udey; Esther von Stebut |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't Date: 2006-04-27 |
Journal Detail:
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Title: The Journal of investigative dermatology Volume: 126 ISSN: 0022-202X ISO Abbreviation: J. Invest. Dermatol. Publication Date: 2006 Jul |
Date Detail:
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Created Date: 2006-06-16 Completed Date: 2006-08-01 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 0426720 Medline TA: J Invest Dermatol Country: United States |
Other Details:
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Languages: eng Pagination: 1582-9 Citation Subset: IM |
Affiliation:
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Department of Dermatology, Johannes Gutenberg-University Mainz, Mainz, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD4 / analysis Disease Progression Gene Expression Regulation / physiology Interferon-gamma / analysis Interleukin-1 / pharmacology, physiology Interleukin-4 / analysis L-Selectin / analysis Leishmania major / immunology* Leishmaniasis, Cutaneous / immunology, pathology, physiopathology* Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Receptors, Interleukin-1 / genetics*, physiology* Receptors, Interleukin-1 Type I Signal Transduction / physiology* T-Lymphocytes, Helper-Inducer / chemistry, pathology Th1 Cells / chemistry, pathology, physiology Th2 Cells / chemistry, pathology, physiology |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD4; 0/Interleukin-1; 0/Receptors, Interleukin-1; 0/Receptors, Interleukin-1 Type I; 126880-86-2/L-Selectin; 207137-56-2/Interleukin-4; 82115-62-6/Interferon-gamma |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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