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

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 paracoccidioi-domycosis. Initially, we verified that P. brasiliensis infection reinforced the tendency of dectin-1–deficient mac-rophages 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 poly-morphonuclear cells to infected tissues. In conclusion, dectin-1 exerts an important protective role in pulmo-nary paracoccidioidomycosis by controlling the innate and adaptive phases of antifungal immunity