Dectin-1 induces M1 macrophages and prominent expansion of CD8+IL-17+ cells in a pulmonary model of fungal infection

• Grant number: 14/06060-8
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: April 01, 2014
• End date: September 30, 2014
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Vera Lucia Garcia Calich
• Grantee: Vera Lucia Garcia Calich
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Dectin-1, the innate immune receptor that recognizes ²-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 ²-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 anti-inflammatory activity of dectin1-/- macrophages resulted in impaired fungicidal ability, low nitric oxide production and elevated synthesis of 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 Th1/Th2/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 PMN neutrophils to infected tissues. In conclusion, dectin-1 exerts an important protective role in pulmonary paracoccidioidomycosis by controlling the innate and adaptive phases of anti-fungal immunity. (AU)