Dendritic cells from X-linked hyper-IgM patients present impaired responses to Candida albicans and Paracoccidioides brasiliensis

Dendritic cells from X-linked hyper-IgM patients present impaired responses to Candida albicans and Paracoccidioides brasiliensis

Author Marques, Otavio Cabral Google Scholar
Arslanian, Christina Google Scholar
Ramos, Rodrigo Nalio Google Scholar
Morato, Mariana Google Scholar
Schimke, LenaFriederike Google Scholar
Soeiro, Paulo Vitor Google Scholar
Jancar, Sonia Google Scholar
Ferreira, Janira Fernandes Google Scholar
Weber, Cristina Worm Google Scholar
Kuntze, Gisele Google Scholar
Rosario-Filho, Nelson Augusto Google Scholar
Costa-Carvalho, Beatriz Tavares Autor UNIFESP Google Scholar
Bergami-Santos, Patricia Cruz Google Scholar
Hackett, Mary J. Google Scholar
Ochs, Hans D. Google Scholar
Torgerson, Troy R. Google Scholar
Marzagao Barbuto, Jose Alexandre Google Scholar
Condino-Neto, Antonio Google Scholar
Institution Universidade de São Paulo (USP)
Pediat Allergy & Immunol Clin
Albert Sabin Hosp
Pequeno Principe Hosp
Univ Fed Parana
Universidade Federal de São Paulo (UNIFESP)
Univ Washington
Seattle Childrens Hosp
Abstract 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-gamma, TGF-beta, 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-g 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. (J Allergy Clin Immunol 2012; 129: 778-86.)
Keywords CD40 ligand deficiency
fungal infections
dendritic cells
X-linked hyper-IgM syndrome
primary immunodeficiency
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Jeffrey Modell Foundation
Grant number FAPESP: 2008/06635-0
FAPESP: 2008/55700-9
FAPESP: 2009/54599-5
Date 2012-03-01
Published in Journal of Allergy and Clinical Immunology. New York: Mosby-Elsevier, v. 129, n. 3, p. 778-786, 2012.
ISSN 0091-6749 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 778-786
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000301189300025

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