Extracellular Vesicles From the Dermatophyte Trichophyton interdigitale Modulate Macrophage and Keratinocyte Functions

Author(s)

Bitencourt, Tamires Aparecida ^[1] ; Rezende, Caroline Patini ^[2] ; Quaresemin, Natalia Renault ^[1] ; Moreno, Pedro ^[2] ; Hatanaka, Otavio ^[2] ; Rossi, Antonio ^[1] ; Martinez-Rossi, Nilce Maria ^[1] ; Almeida, Fausto ^[2]

Affiliation

^[1] Univ Sao Paulo, Dept Genet, Ribeirao Preto Med Sch, Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ribeirao Preto - Brazil

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 9, OCT 9 2018.
• Web of Science Citations: 14

Abstract

The release of biomolecules critically affects all pathogens and their establishment of diseases. For the export of several biomolecules in diverse species, the use of extracellular vesicles (EVs) is considered to represent an alternative transport mechanism, but no study to date has investigated EVs from dermatophytes. Here, we describe biologically active EVs from the dermatophyte Trichophyton interdigitale, a causative agent of mycoses worldwide. EV preparations from T interdigitale were examined using nanoparticle-tracking analysis, which revealed vesicular structures 20-380 nm in diameter. These vesicles induced the production of proinflammatory mediators by bone marrow-derived macrophages (BMDMs) and keratinocytes in a dose-dependent manner, and an addition of the EVs to BMDMs also stimulated the transcription of the M1-polarization marker iNOS (inducible nitric oxide synthase) and diminished the expression of the M2 markers arginase-1 and Ym-1. The observed M1 macrophages' polarization triggered by EVs was abolished in cells obtained from knockout Toll-like receptor-2 mice. Also, the EVs-induced productions of pro-inflammatory mediators were blocked too. Furthermore, the EVs from T interdigitale enhanced the fungicidal activity of BMDMs. These results suggest that EVs from T interdigitale can modulate the innate immune response of the host and influence the interaction between T interdigitale and host immune cells. Our findings thus open new areas of investigation into the host-parasite relationship in dermatophytosis. (AU)

• FAPESP's process: 14/03847-7 - Molecular characterization of mechanisms involved in pathogenicity and cell signaling in fungi
• Grantee: Nilce Maria Martinez-Rossi
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/15055-3 - Role of galectin-3 in the Cryptococcus neoformans infection
• Grantee: Fausto Bruno dos Reis Almeida
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 15/23435-8 - Molecular mechanisms involved in resistance and adaptive response to fungal inhibitors
• Grantee: Tamires Aparecida Bitencourt
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/03322-7 - Role of galectin-3 in the Cryptococcus neoformans infection
• Grantee: Fausto Bruno dos Reis Almeida
• Support Opportunities: Research Grants - Young Investigators Grants