PMID- 30356863 OWN - NLM STAT- MEDLINE DCOM- 20191010 LR - 20220408 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 9 DP - 2018 TI - Extracellular Vesicles From the Dermatophyte Trichophyton interdigitale Modulate Macrophage and Keratinocyte Functions. PG - 2343 LID - 10.3389/fimmu.2018.02343 [doi] LID - 2343 AB - 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. FAU - Bitencourt, Tamires Aparecida AU - Bitencourt TA AD - Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Rezende, Caroline Patini AU - Rezende CP AD - Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Quaresemin, Natalia Renault AU - Quaresemin NR AD - Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Moreno, Pedro AU - Moreno P AD - Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Hatanaka, Otavio AU - Hatanaka O AD - Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Rossi, Antonio AU - Rossi A AD - Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Martinez-Rossi, Nilce Maria AU - Martinez-Rossi NM AD - Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Almeida, Fausto AU - Almeida F AD - Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181009 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 31C4KY9ESH (Nitric Oxide) SB - IM MH - Animals MH - Biomarkers MH - Cytokines/metabolism MH - Disease Models, Animal MH - Extracellular Vesicles/*metabolism MH - Immunomodulation MH - Immunophenotyping MH - Inflammation Mediators/metabolism MH - Keratinocytes/*immunology/*metabolism MH - Macrophage Activation/immunology MH - Macrophages/*immunology/*metabolism/microbiology MH - Male MH - Mice MH - Mice, Knockout MH - Nitric Oxide/metabolism MH - Phagocytosis/immunology MH - Tinea/*immunology/*microbiology MH - Trichophyton/*immunology/*metabolism PMC - PMC6190888 OTO - NOTNLM OT - Trichophyton interdigitale OT - extracellular vesicles OT - fungal infection OT - innate immunity OT - keratinocytes OT - macrophages OT - nanoparticle-tracking analysis EDAT- 2018/10/26 06:00 MHDA- 2019/10/11 06:00 PMCR- 2018/01/01 CRDT- 2018/10/26 06:00 PHST- 2018/06/29 00:00 [received] PHST- 2018/09/20 00:00 [accepted] PHST- 2018/10/26 06:00 [entrez] PHST- 2018/10/26 06:00 [pubmed] PHST- 2019/10/11 06:00 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2018.02343 [doi] PST - epublish SO - Front Immunol. 2018 Oct 9;9:2343. doi: 10.3389/fimmu.2018.02343. eCollection 2018.