IL-10 increases host susceptibility to extracellular bacteria such as Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa in models of primary infections. In addition, IL-10 has a complementary role to IL-4, another macrophage-deactivating cytokine, in the increased susceptibility of mice to murine leishmaniasis [53, 54]. Based on the above, the low level of IL-10 in the mice immunized with pBKTcSPR could improve resistance to infection with T. cruzi. Furthermore,

compared with pBKTcSP and pBKTcSPA, pBKTcSPR does not induce click here IL-2 and IL-5 and promoted lower concentrations of IL-6. Although we do not know exactly why mice immunized with the recombinant protein die after infection with T. cruzi, high serum levels of IL-10 before infection could be considered to be the reason, along with the mixed Th1/Th2 T-cell induced immune response. To better understand the antigen-specific cellular immune responses induced by immunization with the recombinant proteins

and naked DNA before parasite challenge, we are currently conducting experiments to investigate the cytokine production by splenocytes harvested from immunized animals. It is also necessary to implement experiments using anti-IL-10 mAbs or IL-10 KO mice to determine the role that IL-10 plays in the protection-death of vaccinated mice. Some determining factors that favour Th1 vs. Th2 T-cell immune response BTK pathway inhibitors in pathogen infections have been proposed, including the nature of the antigen (intracellular antigens favour Th1 and extracellular antigens favour Th2) and the concentration of antigen (low concentrations favour Th1 and high concentrations favour Th2) [55]. Another factor that affects the immune response is the use of adjuvant; in the present work, we use Freud’s adjuvant for protein immunization, which has the ability to elicit both Th1 and Th2 T-cell immune response. Incomplete Freund’s adjuvant (IFA) was used in human trials; however, it was discontinued as a vaccine adjuvant in humans due to several safety concerns that were determined in animals [56]. Based on this, we are conducting experiments in mice using adjuvants that have been developed

for human use. In these protection Sitaxentan assays, low concentrations of recombinant proteins of TcSP domains are being used to study whether they are able to protect against T. cruzi infection. Alum, CpG and liposomes were selected because they are able stimulate the production of antibodies and cytokines but differ in their mechanism of action: alum acts through APC death, CpG acts through TLR9, and liposomes act through antigen delivery [56]. None of the mice immunized with PBS/adjuvant survived; however, 50% of those immunized with empty plasmid did survive – despite parasitemia being similar (97 × 104 vs. 91 × 104). The survival may be due to the response induced by immunostimulatory sequences in the plasmid that trigger innate immunity in the host [57].