Immune regulatory effect of pHSP65 DNA therapy in pulmonary tuberculosis: activation of CD8+ cells, interferon-gamma recovery and reduction of lung injury.
A DNA vaccine based on the heat-shock protein 65 Mycobacterium leprae gene (pHSP65) presented a prophylactic and therapeutic effect in an experimental model of tuberculosis. In this paper, we addressed the question of which protective mechanisms are activated in Mycobacterium tuberculosis-infected mice after immune therapy with pHSP65. We evaluated activation of the cellular immune response in the lungs of infected mice 30 days after infection (initiation of immune therapy) and in those of uninfected mice. After 70 days (end of immune therapy), the immune responses of infected untreated mice, infected pHSP65-treated mice and infected pCDNA3-treated mice were also evaluated. Our results show that the most significant effect of pHSP65 was the stimulation of CD8+ lung cell activation, interferon-gamma recovery and reduction of lung injury. There was also partial restoration of the production of tumour necrosis factor-alpha. Treatment with pcDNA3 vector also induced an immune stimulatory effect. However, only infected pHSP65-treated mice were able to produce significant levels of interferon-gamma and to restrict the growth of bacilli.
Bonato
V L D
VL
TB Network, Department of Biochemistry and Immunology, Ribeirao Preto School of Medicine, University of Sao Paulo, Brazil. vlbonato@fmrp.usp.br
Gonçalves
E D C
ED
Soares
E G
EG
Santos Júnior
R R
RR
Sartori
A
A
Coelho-Castelo
A A M
AA
Silva
C L
CL
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D018821:CD18 Antigens / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018834:Chaperonin 60; D018833:Chaperonins / Q000235:genetics*; D053222:Fas Ligand Protein; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D015854:Up-Regulation; D019444:Vaccines, DNA / Q000627:therapeutic use*; D019014:fas Receptor / Q000378:metabolism
D001426:Bacterial Proteins; D018821:CD18 Antigens; D018106:CD28 Antigens; D018834:Chaperonin 60; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019444:Vaccines, DNA; D019014:fas Receptor; C074119:heat-shock protein 65, Mycobacterium; D007371:Interferon-gamma; D018833:Chaperonins