Details

Autor(en) / Beteiligte

• Marques, Otavio Cabral, MSc
• Arslanian, Christina, BSc
• Ramos, Rodrigo Nalio, MSc
• Morato, Mariana, MSc
• Schimke, LenaFriederike, MD
• Soeiro Pereira, Paulo Vitor, MSc
• Jancar, Sonia, MD, PhD
• Ferreira, Janaíra Fernandes, MD
• Weber, Cristina Worm, MD
• Kuntze, Gisele, MD
• Rosario-Filho, Nelson Augusto, MD, PhD
• Costa Carvalho, Beatriz Tavares, MD
• Bergami-Santos, Patricia Cruz, PhD
• Hackett, Mary J., BSc
• Ochs, Hans D., MD
• Torgerson, Troy R., MD, PhD
• Barbuto, Jose Alexandre Marzagão, MD, PhD
• Condino-Neto, Antonio, MD, PhD

Titel

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

Ist Teil von

• Journal of allergy and clinical immunology, 2012-03, Vol.129 (3), p.778-786

Ort / Verlag

New York, NY: Mosby, Inc

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 (TH ) 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 TH 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.