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: Flávio V Loures, Eliseu F Araújo, Claudia Feriotti, Silvia B Bazan, Tânia A Costa, Gordon D Brown, Vera L G Calich
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 210 Issue 5 Pg. 762-73 (Sep 01 2014) ISSN: 1537-6613 [Electronic] United States
• PMID: 24604821 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Interleukin-17
• Lectins, C-Type
• dectin 1

Topics

• Animals
• CD8-Positive T-Lymphocytes (chemistry, immunology)
• Cell Proliferation
• Cells, Cultured
• Disease Models, Animal
• Interleukin-17 (metabolism)
• Lectins, C-Type (metabolism)
• Macrophages (immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Paracoccidioides (immunology)
• Paracoccidioidomycosis (immunology, pathology)
• Survival Analysis
• T-Lymphocytes, Regulatory (chemistry, immunology)