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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Dectin-1 Induces M1 Macrophages and Prominent Expansion of CD8(+)IL-17(+) Cells in Pulmonary Paracoccidioidomycosis

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Autor(es):
Loures, Flavio V. [1] ; Araujo, Eliseu F. [1] ; Feriotti, Claudia [1] ; Bazan, Silvia B. [1] ; Costa, Tania A. [1] ; Brown, Gordon D. [2] ; Calich, Vera L. G. [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508900 Sao Paulo - Brazil
[2] Univ Aberdeen, Inst Med Sci, Sect Immun & Infect, Aberdeen Fungal Grp, Aberdeen AB9 1FX - Scotland
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: Journal of Infectious Diseases; v. 210, n. 5, p. 762-773, SEP 1 2014.
Citações Web of Science: 29
Resumo

Dectin-1, the innate immune receptor that recognizes beta-glucan, plays an important role in immunity against fungal pathogens. Paracoccidioides brasiliensis, the etiological agent of paracoccidioidomycosis, has a sugar-rich cell wall mainly composed of mannans and glucans. This fact motivated us to use dectin-1-sufficient and deficient mice to investigate the role of beta-glucan recognition in the immunity against pulmonary paracoccidioidomycosis. Initially, we verified that P. brasiliensis infection reinforced the tendency of dectin-1-deficient macrophages to express an M2 phenotype. This prevalent antiinflammatory activity of dectin-1(-/-) macrophages resulted in impaired fungicidal ability, low nitric oxide production, and elevated synthesis of interleukin 10 (IL-10). Compared with dectin-1-sufficient mice, the fungal infection of dectin-1(-/-) mice was more severe and resulted in enhanced tissue pathology and mortality rates. The absence of dectin-1 has also impaired the production of T-helper type 1 (Th1), Th2, and Th17 cytokines and the activation and migration of T cells to the site of infection. Remarkably, dectin-1 deficiency increased the expansion of regulatory T cells and reduced the differentiation of T cells to the IL-17(+) phenotype, impairing the migration of IL-17(+)CD8(+) T cells and polymorphonuclear cells to infected tissues. In conclusion, dectin-1 exerts an important protective role in pulmonary paracoccidioidomycosis by controlling the innate and adaptive phases of antifungal immunity. (AU)

Processo FAPESP: 10/52275-5 - Influência dos receptores de imunidade inata (TLR2, TLR4 e Dectina-1) no comportamento de células dendríticas e na determinação do padrão de imunidade adaptativa dos hospedeiros contra o paracocciodióides
Beneficiário:Vera Lucia Garcia Calich
Modalidade de apoio: Auxílio à Pesquisa - Regular