Therapeutic DNA vaccine reduces schistosoma mansoni-induced tissue damage through cytokine balance and decreased migration of myofibroblasts

Am J Pathol. 2011 Jul;179(1):223-9. doi: 10.1016/j.ajpath.2011.03.012. Epub 2011 May 18.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Movement*
  • Cell Proliferation
  • Cytokines / metabolism*
  • Female
  • Fibrosis / immunology
  • Fibrosis / metabolism
  • Fibrosis / prevention & control*
  • Fluorescent Antibody Technique
  • Granuloma / immunology
  • Granuloma / metabolism
  • Granuloma / prevention & control*
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Myofibroblasts / immunology
  • Myofibroblasts / metabolism
  • Myofibroblasts / pathology*
  • Ovum / immunology
  • Ovum / metabolism
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Schistosoma mansoni / genetics
  • Schistosoma mansoni / immunology
  • Schistosomiasis mansoni / immunology
  • Schistosomiasis mansoni / metabolism
  • Schistosomiasis mansoni / prevention & control*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Th2 Cells / pathology
  • Vaccines, DNA / therapeutic use*

Substances

  • Cytokines
  • RNA, Messenger
  • Vaccines, DNA