title: Dectin-1 induces M1 macrophages and prominent expansion of CD8+IL-17+ cells in pulmonary Paracoccidioidomycosis.
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.
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
authors.forename: Flávio V
authors.initials: FV
authors.lastname: Loures
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
authors.forename: Eliseu F
authors.initials: EF
authors.lastname: Araújo
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
authors.forename: Claudia
authors.initials: C
authors.lastname: Feriotti
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
authors.forename: Silvia B
authors.initials: SB
authors.lastname: Bazan
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
authors.forename: Tânia A
authors.initials: TA
authors.lastname: Costa
authors.affiliation: Aberdeen Fungal Group, Section of Immunity and Infection, Institute of Medical Sciences, University of Aberdeen, United Kingdom.
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
authors.forename: Vera L G
authors.initials: VL
authors.lastname: Calich
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010228:Paracoccidioides / Q000276:immunology*; D010229:Paracoccidioidomycosis / Q000276:immunology* / Q000473:pathology; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology; D000099181:Dectin-1
chemical_list: D020381:Interleukin-17; D037181:Lectins, C-Type; D000099181:Dectin-1
keywords: Paracoccidioides brasiliensis; adaptive immunity; dectin-1 receptor; innate immunity; pulmonary pathology