Protective efficacy of different strategies employingMycobacterium lepraeheat-shock protein 65 against tuberculosis

Evaluation of the overall IFN-γ and IL-17 pro-inflammatory responses after DNA therapy of tuberculosis

“…For this reason, we evaluated the number of anti-Hsp65-specific T lymphocytes that secrete IFN-γ, a key effector cytokine for combating M. tuberculosis. As previously described in prophylactic studies on M. tuberculosis 7 as well as after short-term tuberculosis therapy, 8 we observed an increase in the number of anti-Hsp65-specific T cells that secrete IFN-γ in the lungs of DNA-hsp65-treated mice during short and long follow-up after therapy completion ( Fig. 2A).…”

“…Female, Specific Pathogen-Free, BALB/c mice (8 weeks old) from the local animal facility were anaesthetized with 10% ketamine chloridrate (100 mg/Kg) and 2% xylazine chloridrate (20 mg/ Kg) (Agener União) and infected on day 0 with 1.0 × 10 5 bacilli of the M. tuberculosis H37Rv strain via the intra-tracheal route, as previously described. 7,62 Thirty days after infection, the mice began treatment with 100 μg of DNA-hsp65, in a final volume of 100 μl (25% sucrose), receiving 50 μl in each quadriceps at 10-d intervals until day 60 (total of four doses). The mice were euthanized by cervical dislocation at either day 70 or 120 after infection, corresponding to 10 and 60 d after completing immunotherapy, respectively.…”

“…The morphometric analysis was performed following recommendations as described before. 7,63 Briefly, left lungs from mice at days 10 and 60 after infection, were inflated and used to obtain paraffin sections that were stained with hematoxylin-eosin and evaluated by a pathologist in a single-blinded manner. The morphometric analysis was performed using a conventional light microscope (Axioplan) with an integrated eyepiece and a system made of a 100-point grid consisting of 10 × 10 lines of known length.…”

“…These results stress the importance of a broad evaluation of not only the specific immune response at the time to evaluate new immune interventional strategies against tuberculosis but also non-conventional T cells, such as γδ T lymphocytes. 3 Extensive evidence demonstrated that this molecule can protect against a subsequent challenge by M. tuberculosis [5][6][7] and can also treat the active disease by stimulating strong anti-Hsp65-specific IFN-γ-secreting Th1 cells, increasing the activity of cytotoxic CD8 + lymphocytes and reducing the bacterial loads. [8][9][10] The reduction of lung inflammation in DNA-hsp65-treated mice has also been observed with this strong pro-inflammatory response.…”

Expression of Mycobacterium leprae HSP65 in tobacco and its effectiveness as an oral treatment in adjuvant-induced arthritis

“…The gene for HSP65 of Mycobacterium leprae has been shown to have immunomodulatory effects in various diseases, including the inhibition of the development of different types of tumor cells (Lukcas et al 1993;Michaluart et al 2008), the development of prophylactics against tuberculosis (Jones et al 1993;Rosada et al 2008;Souza et al 2008;Zárate-Bladés et al 2009) in systemic fungal infection (Ribeiro et al 2009) and, potentially, the modulation of arthritis, diabetes and multiple sclerosis (van Eden et al 1985;Life et al 1993;Matzinger 1994;Chen et al 1999;Quintana et al 2003;Santos-Júnior et al 2007). In arthritic rats, the purified HSP65 protein co-administered orally with soybean trypsin inhibitor at low doses (30 mg) has been shown to play an important role in the modulation of arthritis induced by adjuvant (AIA).…”