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

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Marques, Otavio Cabral ^{[1, 2, 3]} ; Arslanian, Christina ^[1] ; Ramos, Rodrigo Nalio ^[1] ; Morato, Mariana ^[1] ; Schimke, LenaFriederike ^{[1, 2, 3]} ; Soeiro, Paulo Vitor ^[1] ; Jancar, Sonia ^[1] ; Ferreira, Janira Fernandes ^[4] ; Weber, Cristina Worm ^[5] ; Kuntze, Gisele ^[6] ; Rosario-Filho, Nelson Augusto ^[7] ; Costa Carvalho, Beatriz Tavares ^[8] ; Bergami-Santos, Patricia Cruz ^[1] ; Hackett, Mary J. ^{[2, 3]} ; Ochs, Hans D. ^{[2, 3]} ; Torgerson, Troy R. ^{[2, 3]} ; Marzagao Barbuto, Jose Alexandre ^[1] ; Condino-Neto, Antonio ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, BR-05508000 Sao Paulo - Brazil

^[2] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 - USA

^[3] Seattle Childrens Hosp, Seattle, WA - USA

^[4] Albert Sabin Hosp, Fortaleza, Ceara - Brazil

^[5] Pediat Allergy & Immunol Clin, Caxias Do Sul - Brazil

^[6] Pequeno Principe Hosp, Curitiba, Parana - Brazil

^[7] Univ Fed Parana, Dept Pediat, Sch Med, BR-80060000 Curitiba, Parana - Brazil

^[8] Univ Fed Sao Paulo, Dept Pediat, Div Allergy Immunol & Rheumatol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Allergy and Clinical Immunology; v. 129, n. 3, p. 778-786, MAR 2012.
• Citações Web of Science: 15

Resumo

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.) (AU)

• Processo FAPESP: 08/55700-9 - Defeitos genetico-moleculares e aspectos clinicos de pacientes com sindrome da hiper-igm autossomica.
• Beneficiário: Stefanie Klaver Flores
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 09/54599-5 - Células dendríticas: elementos integrados do sistema imune - enfoque aplicado
• Beneficiário: Jose Alexandre Marzagão Barbuto
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 08/06635-0 - Estudo dos Mecanismos Moleculares e Celulares da Imunidade Inata que Regem a Fisio-Patologia da Asma
• Beneficiário: Leonardo Varuzza
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico