Experimental tuberculosis: designing a better model to test vaccines against tuberculosis.
Experimental models of infection are good tools for establishing immunological parameters that have an effect on the host-pathogen relationship and also for designing new vaccines and immune therapies. In this work, we evaluated the evolution of experimental tuberculosis in mice infected with increasing bacterial doses or via distinct routes. We showed that mice infected with low bacterial doses by the intratracheal route were able to develop a progressive infection that was proportional to the inoculum size. In the initial phase of disease, mice developed a specific Th1-driven immune response independent of inoculum concentration. However, in the late phase, mice infected with higher concentrations exhibited a mixed Th1/Th2 response, while mice infected with lower concentrations sustained the Th1 pattern. Significant IL-10 concentrations and a more preeminent T regulatory cell recruitment were also detected at 70 days post-infection with high bacterial doses. These results suggest that mice infected with higher concentrations of bacilli developed an immune response similar to the pattern described for human tuberculosis wherein patients with progressive tuberculosis exhibit a down modulation of IFN-gamma production accompanied by increased levels of IL-4. Thus, these data indicate that the experimental model is important in evaluating the protective efficacy of new vaccines and therapies against tuberculosis.
Morais Fonseca
Denise
D
Núcleo de Pesquisas em Tuberculose, Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes, 3900, CEP 14049-900 Ribeirão Preto, SP, Brazil. denise@cpt.fmrp.usp.br <denise@cpt.fmrp.usp.br>
Rosada
Rogério Silva
RS
e Paula
Marina Oliveira
MO
Wowk
Pryscilla Fanini
PF
Franco
Luis Henrique
LH
Soares
Edson Garcia
EG
Silva
Célio Lopes
CL
Deperon Bonato
Vânia Luiza
VL
D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D007167:Immunotherapy; D007371:Interferon-gamma / Q000276:immunology*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000494:pharmacology*
D032581:Tuberculosis Vaccines; D007371:Interferon-gamma