Helminth coinfection does not affect therapeutic effect of a DNA vaccine in mice harboring tuberculosis.
BACKGROUND
Helminthiasis and tuberculosis (TB) coincide geographically and there is much interest in exploring how concurrent worm infections might alter immune responses against bacilli and might necessitate altered therapeutic approaches. A DNA vaccine that codifies heat shock protein Hsp65 from M. leprae (DNAhsp65) has been used in therapy during experimental tuberculosis. This study focused on the impact of the co-existence of worms and TB on the therapeutic effects of DNAhsp65.


RESULTS
Mice were infected with Toxocara canis or with Schistosoma mansoni, followed by coinfection with M. tuberculosis and treatment with DNAhsp65. While T. canis infection did not increase vulnerability to pulmonary TB, S. mansoni enhanced susceptibility to TB as shown by higher numbers of bacteria in the lungs and spleen, which was associated with an increase in Th2 and regulatory cytokines. However, in coinfected mice, the therapeutic effect of DNAhsp65 was not abrogated, as indicated by colony forming units and analysis of histopathological changes. In vitro studies indicated that Hsp65-specific IFN-gamma production was correlated with vaccine-induced protection in coinfected mice. Moreover, in S. mansoni-coinfected mice, DNA treatment inhibited in vivo TGF-beta and IL-10 production, which could be associated with long-term protection.


CONCLUSIONS
We have demonstrated that the therapeutic effects of DNAhsp65 in experimental TB infection are persistent in the presence of an unrelated Th2 immune response induced by helminth infections.
Frantz
Fabiani G
FG
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Rosada
Rogério S
RS
Peres-Buzalaf
Camila
C
Perusso
Franciele R T
FR
Rodrigues
Vanderlei
V
Ramos
Simone G
SG
Kunkel
Steven L
SL
Silva
Célio L
CL
Faccioli
Lúcia H
LH
D000704:Analysis of Variance; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D018834:Chaperonin 60 / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006376:Helminths; D007371:Interferon-gamma; D007378:Interleukins / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009573:Nitrites / Q000378:metabolism; D012550:Schistosoma mansoni; D012555:Schistosomiasis mansoni / Q000276:immunology / Q000382:microbiology*; D018417:Th1 Cells / Q000378:metabolism; D017166:Toxocara canis; D014120:Toxocariasis / Q000382:microbiology*; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology* / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000276:immunology* / Q000494:pharmacology; D019444:Vaccines, DNA / Q000276:immunology* / Q000494:pharmacology
D001426:Bacterial Proteins; D018834:Chaperonin 60; D007378:Interleukins; D009573:Nitrites; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; C074119:heat-shock protein 65, Mycobacterium; D007371:Interferon-gamma