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Title: Dendritic cells from X-linked hyper-IgM patients present impaired responses to Candida albicans and Paracoccidioides brasiliensis
Authors: Marques, Otavio Cabral
Arslanian, Christina
Ramos, Rodrigo Nalio
Morato, Mariana
Schimke, LenaFriederike
Soeiro, Paulo Vitor
Jancar, Sonia
Ferreira, Janira Fernandes
Weber, Cristina Worm
Kuntze, Gisele
Rosario-Filho, Nelson Augusto
Costa-Carvalho, Beatriz Tavares [UNIFESP]
Bergami-Santos, Patricia Cruz
Hackett, Mary J.
Ochs, Hans D.
Torgerson, Troy R.
Marzagao Barbuto, Jose Alexandre
Condino-Neto, Antonio
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
Keywords: CD40 ligand deficiency
fungal infections
dendritic cells
X-linked hyper-IgM syndrome
primary immunodeficiency
Issue Date: 1-Mar-2012
Publisher: Elsevier B.V.
Citation: Journal of Allergy and Clinical Immunology. New York: Mosby-Elsevier, v. 129, n. 3, p. 778-786, 2012.
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.)
ISSN: 0091-6749
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