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J Infect Dis. 2014 Sep 1;210(5):762-73. doi: 10.1093/infdis/jiu136. Epub 2014 Mar 5.

Dectin-1 induces M1 macrophages and prominent expansion of CD8+IL-17+ cells in pulmonary Paracoccidioidomycosis.

Author information

1
Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
2
Aberdeen Fungal Group, Section of Immunity and Infection, Institute of Medical Sciences, University of Aberdeen, United Kingdom.

Abstract

Dectin-1, the innate immune receptor that recognizes β-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 β-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.

KEYWORDS:

Paracoccidioides brasiliensis; adaptive immunity; dectin-1 receptor; innate immunity; pulmonary pathology

PMID:
24604821
DOI:
10.1093/infdis/jiu136
[Indexed for MEDLINE]

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