title: DNA vaccine encoding peptide P10 against experimental paracoccidioidomycosis induces long-term protection in presence of regulatory T cells.
abstract: Paracoccidioidomycosis is a granulomatous systemic mycosis endemic in Brazil and other Latin America countries. A DNA vaccine encoding the immunoprotective peptide 10 (P10) significantly reduced the fungal burden in mice when given prior to or after intratracheal challenge with Paracoccidioides brasiliensis. Presently, the generation/expansion of CD4+ CD44hi memory T cells as well as Foxp3+ Treg cells in mice immunized with the DNA vaccine (pcDNA3-P10) before and after infection with P. brasiliensis was investigated. Memory CD4+ CD44hi T cells simultaneously with Foxp3+ Treg cells increased in the spleens and lungs of pcDNA3-P10 immunized mice on day 0, 30, 60 and 120 postinfection. Histopathology of the lung tissue showed minimal inflammation in immunized mice compared with the unimmunized group, suggesting a role for regulatory T cells in controlling the immunopathology. The DNA vaccine shows that the repeated immunization generates memory cells and regulatory T cells that replace the initially protective pro-inflammatory T cells conferring a long term protection while preserving the integrity of the infected tissue.
authors.affiliation: Institute of Biomedical Sciences, Department of Microbiology, University of São Paulo, Av. Prof. Lineu Prestes, 1374, São Paulo, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: de Amorim
authors.forename: Adriana
authors.initials: A
authors.lastname: Magalhães
authors.forename: Julián Esteban
authors.initials: JE
authors.lastname: Muñoz
authors.forename: Glauce M G
authors.initials: GM
authors.lastname: Rittner
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Nosanchuk
authors.forename: Luiz R
authors.initials: LR
authors.lastname: Travassos
authors.forename: Carlos P
authors.initials: CP
authors.lastname: Taborda
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000473:pathology; D008172:Lung Diseases, Fungal / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010229:Paracoccidioidomycosis / Q000276:immunology / Q000517:prevention & control*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*
chemical_list: C476399:Cd44 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C550731:P10 peptide, Paracoccidioides brasiliensis; D010446:Peptide Fragments; D019444:Vaccines, DNA