Dectin-1 induces M1 macrophages and prominent expansion of CD8+IL-17+ cells in pulmonary Paracoccidioidomycosis

Flávio V Loures, Eliseu F Araújo, Claudia Feriotti, Silvia B Bazan, Tânia A Costa, Gordon D Brown, Vera L G Calich

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36 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)762-773
Number of pages12
JournalThe journal of infectious diseases
Volume210
Issue number5
Early online date5 Mar 2014
DOIs
Publication statusPublished - 1 Sep 2014

Keywords

  • Animals
  • CD8-Positive T-Lymphocytes
  • Cell Proliferation
  • Cells, Cultured
  • Disease Models, Animal
  • Interleukin-17
  • Lectins, C-Type
  • Macrophages
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Paracoccidioides
  • Paracoccidioidomycosis
  • Survival Analysis
  • T-Lymphocytes, Regulatory
  • Paracoccidioides Brasiliensis
  • Dectin-1 Receptor
  • Innate Immunity
  • Pulmonary Pathology
  • Adaptive Immunity

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    Loures, F. V., Araújo, E. F., Feriotti, C., Bazan, S. B., Costa, T. A., Brown, G. D., & Calich, V. L. G. (2014). Dectin-1 induces M1 macrophages and prominent expansion of CD8+IL-17+ cells in pulmonary Paracoccidioidomycosis. The journal of infectious diseases, 210(5), 762-773. https://doi.org/10.1093/infdis/jiu136