| Full text | |
| Author(s): Show less - |
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]
Total Authors: 18
|
| Affiliation: | [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
Total Affiliations: 8
|
| Document type: | Journal article |
| Source: | Journal of Allergy and Clinical Immunology; v. 129, n. 3, p. 778-786, MAR 2012. |
| Web of Science Citations: | 15 |
| 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.) (AU) | |
| FAPESP's process: | 09/54599-5 - Dendritic cells: integrative elements of the immune system - an applied approach |
| Grantee: | Jose Alexandre Marzagão Barbuto |
| Support Opportunities: | Research Projects - Thematic Grants |