title: Therapeutic DNA vaccine reduces schistosoma mansoni-induced tissue damage through cytokine balance and decreased migration of myofibroblasts.
abstract: Helminths are known to elicit a wide range of immunomodulation characterized by dominant Th2-type immune responses. Our group previously showed that a DNA vaccine encoding the mycobacterial 65-kDa heat shock protein (DNA-hsp65) showed immunomodulatory properties. We also showed, using a helminth-tuberculosis (TB) co-infection model, that the DNA-hsp65 vaccine protected mice against TB. We next investigated the mechanistic role of the vaccine during helminth-TB co-infection. Clinically, helminth infection causes type 2 granulomas in the lung. Mice were immunized with DNA-hsp65 while they were submitted to the type 2 granuloma induction protocol by Schistosoma mansoni eggs infusion. In this work we investigated the effects of DNA-hsp65 on the pathology and immune response during the development of type 2 granuloma induced by S. mansoni eggs. Histologic analyses of lung parenchyma showed that the DNA-hsp65 vaccine protected mice against exacerbated fibrosis induced by Schistosoma eggs, and decreased the size of the granulomas. These changes were correlated with a reduction in the number of T cells specific for the egg antigens in the lung and also with modulation of Th2 cytokine expression. Taken together, our results showed that the adjuvant properties of the DNA-hsp65 vaccine regulated the immune response in this Th2 model, and resulted in a preserved lung parenchyma.
authors.affiliation: Department of Clinical Analyses, Toxicology and Bromatologics, Ribeirão Preto College of Pharmaceutical Sciences, University of São Paulo-Ribeirão Preto, São Paulo, Brazil.
authors.forename: Fabiani Gai
authors.initials: FG
authors.lastname: Frantz
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ito
authors.forename: Karen Angélica
authors.initials: KA
authors.lastname: Cavassani
authors.forename: Cory M
authors.initials: CM
authors.lastname: Hogaboam
authors.forename: Célio
authors.initials: C
authors.lastname: Lopes Silva
authors.forename: Steven L
authors.initials: SL
authors.lastname: Kunkel
authors.forename: Lúcia H
authors.initials: LH
authors.lastname: Faccioli
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005355:Fibrosis / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D005455:Fluorescent Antibody Technique; D006099:Granuloma / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D058628:Myofibroblasts / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010063:Ovum / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012550:Schistosoma mansoni / Q000235:genetics / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019444:Vaccines, DNA / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D019444:Vaccines, DNA