| Full text | |
| Author(s): Show less - |
Rodrigues, Rodrigo F.
[1]
;
Zarate-Blades, Carlos R.
[1]
;
Rios, Wendy M.
[1]
;
Soares, Luana S.
[1]
;
Souza, Patricia R. M.
[1]
;
Brandao, Izaira T.
[1]
;
Masson, Ana P.
[1]
;
Arnoldi, Frederico G. C.
[1]
;
Ramos, Simone G.
[2]
;
Letourneur, Franck
[3, 4]
;
Jacques, Sebastien
[3, 4]
;
Cagnard, Nicolas
[3, 4, 5]
;
Chiocchia, Gilles
[3, 4]
;
Silva, Celio L.
[1]
Total Authors: 14
|
| Affiliation: | [1] Univ Sao Paulo, Ctr TB Res, Dept Biochem & Immunol, Ribeirao Preto Sch Med, BR-14049900 Ribeirao Preto - Brazil
[2] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Pathol, BR-14049900 Sao Paulo - Brazil
[3] Univ Paris 05, Inst Cochin, F-75014 Paris - France
[4] CNRS CMRS 8104, INSERM U1016, F-75014 Paris - France
[5] Hop Necker Enfants Malad, F-75015 Paris - France
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | Journal of Antimicrobial Chemotherapy; v. 70, n. 6, p. 1774-1783, JUN 2015. |
| Web of Science Citations: | 2 |
| Abstract | |
Objectives: Although TB immunotherapy improves the results of conventional drug treatment, the effects of combining chemotherapy and immunotherapy have never been systematically evaluated. We used a comprehensive lung transcriptome analysis to directly compare the activity of combined chemotherapy and immunotherapy with that of single treatments in a mouse model of TB. Methods: Mycobacterium tuberculosis-infected mice in the chronic phase of the disease (day 30) received: (i) isoniazid and rifampicin (drugs) daily for 30 days; (ii) DNA immunotherapy (DNA), consisting of four 100 mu g injections at 10 day intervals; (iii) both therapies (DNA+ drugs); or (iv) saline. The effects were evaluated 10 days after the end of treatment (day 70 post-infection). Results: In all groups a systemic reduction in the load of bacilli was observed, bacilli became undetectable in the drugs and DNA+ drugs groups, but the whole lung transcriptome analysis showed 867 genes exclusively modulated by the DNA+ drugs combination. Gene enrichment analysis indicated that DNA+ drugs treatment provided synergistic effects, including the down-regulation of proinflammatory cytokines and mediators of fibrosis, as confirmed by real-time PCR, ELISA, histopathology and hydroxyproline assay. Conclusions: Our results provide a molecular basis for the advantages of TB treatment using combined chemotherapy and DNA immunotherapy and demonstrate the synergistic effects obtained with this strategy. (AU) | |