| Dendritic cells from X-linked hyper-IgM patients present impaired responses to Candida albicans and Paracoccidioides brasiliensis. | |
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MedLine Citation:
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PMID: 22154528 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: Patients with X-linked hyper-IgM syndrome (X-HIGM) due to CD40 ligand (CD40L) mutations are susceptible to fungal pathogens; however, the underlying susceptibility mechanisms remain poorly understood. OBJECTIVE: To determine whether monocyte-derived dendritic cells (DCs) from patients with X-HIGM exhibit normal responses to fungal pathogens. METHODS: DCs from patients and controls were evaluated for the expression of costimulatory (CD80 and CD86) and MHC class II molecules and for their ability to produce IL-12 and IL-10 in response to Candida albicans and Paracoccidioides brasiliensis. We also evaluated the ability of C albicans- and P brasiliensis-pulsed mature DCs to induce autologous T-cell proliferation, generation of T helper (T(H)) 17 cells, and production of IFN-γ, TGF-β, IL-4, IL-5, and IL-17. RESULTS: Immature DCs from patients with X-HIGM showed reduced expression of CD80, CD86, and HLA-DR, which could be reversed by exogenous trimeric soluble CD40L. Most important, mature DCs from patients with X-HIGM differentiated by coculturing DCs with fungi secreted minimal amounts of IL-12 but substantial amounts of IL-10 compared with mature DCs from normal individuals. Coculture of mature DCs from X-HIGM patients with autologous T cells led to low IFN-γ production, whereas IL-4 and IL-5 production was increased. T-cell proliferation and IL-17 secretion were normal. Finally, in vitro incubation with soluble CD40L reversed the decreased IL-12 production and the skewed T(H)2 pattern response. CONCLUSION: Absence of CD40L during monocyte/DC differentiation leads to functional DC abnormalities, which may contribute to the susceptibility to fungal infections in patients with X-HIGM. |
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Authors:
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Otavio Cabral Marques; Christina Arslanian; Rodrigo Nalio Ramos; Mariana Morato; Lenafriederike Schimke; Paulo Vitor Soeiro Pereira; Sonia Jancar; Janaíra Fernandes Ferreira; Cristina Worm Weber; Gisele Kuntze; Nelson Augusto Rosario-Filho; Beatriz Tavares Costa Carvalho; Patricia Cruz Bergami-Santos; Mary J Hackett; Hans D Ochs; Troy R Torgerson; Jose Alexandre Marzagão Barbuto; Antonio Condino-Neto |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-9 |
Journal Detail:
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Title: The Journal of allergy and clinical immunology Volume: - ISSN: 1097-6825 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1275002 Medline TA: J Allergy Clin Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved. |
Affiliation:
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Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Department of Pediatrics, University of Washington School of Medicine and Seattle Children's Hospital, Seattle. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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