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

• Published in: The Journal of infectious diseases 2014-09, Vol.210 (5), p.762-773
• Main Authors: Loures, Flávio V., Araújo, Eliseu F., Feriotti, Claudia, Bazan, Silvia B., Costa, Tânia A., Brown, Gordon D., Calich, Vera L. G.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blastomycoses and paracoccidioidomycosis; CD8-Positive T-Lymphocytes - chemistry; CD8-Positive T-Lymphocytes - immunology; Cell Proliferation; Cells, Cultured; Cytokines; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Fungal infections; FUNGI; Human mycoses; Immunity; Infections; Infectious diseases; Interleukin-17 - metabolism; Interleukins; Lectins, C-Type - metabolism; Macrophages; Macrophages - immunology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbiology; Mycoses; Paracoccidioides - immunology; Paracoccidioidomycosis; Paracoccidioidomycosis - immunology; Paracoccidioidomycosis - pathology; Receptors; Survival Analysis; T lymphocytes; T-Lymphocytes, Regulatory - chemistry; T-Lymphocytes, Regulatory - immunology; Tropical mycoses; Yeasts
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiu136

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 polymorphonudear 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.