The vaccine Bacillus of Calmette Guérin (BCG)
This study evaluated the immune response to three synthetic peptides (pI, VMVEQVICFD; pII, VGGGLCFE; pIII, PYFLGSIMNTCHYT) from the COOH-terminal region of Leishmania amazonensis cysteine proteinases, in BALB/c- and CBA-infected mice with this parasite. Only BALB/c mice, previously inoculated with pI, showed a distinct exacerbation of the lesion. Blastogenesis assays were performed with lymph node cells from the group of mice infected with L. amazonensis, but not inoculated with the peptides, and we detected lymphoproliferative responses in BALB/c and CBA mice with a 5.0x and 2.5x stimulation index, respectively. Cell phenotypes were evaluated and in both mouse strains CD8(+)cells proliferated more extensively than CD4(+)cells. INF-gamma and nitric oxide were detected only in supernatants obtained from CBA mouse lymph node cell cultures, whereas IL-4 was detected in supernatant cultures from both strains of mice. Our results indicate a preferential stimulation of CD8(+)T-cell subsets by the pI cysteine proteinase peptide and the induction of both Th1 and Th2 phenotypes during L. amazonensis infections in both BALB/c and CBA mice. We suggest that the pI peptide from the COOH-terminal region of the cysteine proteinase induces immune responses different from those elicited by the whole molecule.
Treatment for tuberculosis is effective with the use of proper antibiotics, but the number of drug-resistant cases is increasing. Drug resistance occurred in 650,000 cases of the 20 million patients in treatment worldwide in 2011, which demonstrates the necessity of finding new therapeutic approaches. In this context, the search for new medicines and immunomodulators could help reduce the prevalence and incidence of multi-drug-resistant tuberculosis cases. Thus several preclinical studies demonstrate the involvement of the P2X7 receptor (P2X7R) in the control of Mycobacterium tuberculosis (MTB) infection. Adenosine triphosphate (ATP), a natural agonist for P2X7R, promotes MTB death and the induction of apoptosis in monocytes and macrophages infected with MTB via activation of P2X7R by extracellular ATP. In addition, P2X7R activation in the presence of ATP increases the expression of major histocompatibility complex (MHC) class II by macrophages infected with Mycobacterium bovis (BCG) or MTB, which contributes to the generation of the antimicrobial immune response via T cells. Nevertheless, one idea that seems overlooked by the “purinergic community” is the use of the high-conductance channel associated with P2X7R to increase the passage of hydrophilic drugs to the cytoplasm of cells that express the P2X7 pore, a potential method for a drug delivery system. In this work, we propose the use of P2X7 agonists in conjunction with low molecular weight anti-tuberculosis medicines for the treatment of multi-drug-resistant tuberculosis.
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