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

作者：Loures Flavio V; Araujo Eliseu F; Feriotti Claudia; Bazan Silvia B; Costa Tania A; Brown Gordon D; Calich Vera L G^*

来源：Journal of Infectious Diseases, 2014, 210(5): 762-773.

DOI：10.1093/infdis/jiu136

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

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.

• 出版日期2014-9-1
• 单位河北医科大学