BackgroundPrevious findings indicate that susceptibility to Leishmania (Viannia) panamensis infection of monocyte-derived macrophages from patients and asymptomatically infected individuals were associated with the adaptive immune response and clinical outcome.Methodology/Principal FindingsTo understand the basis for this difference we examined differential gene expression of human monocyte-derived macrophages following exposure to L. (V.) panamensis. Gene activation profiles were determined using macrophages from healthy volunteers cultured with or without stationary phase promastigotes of L. (V.) panamensis. Significant changes in expression (>1.5-fold change; p<0.05; up- or down-regulated) were identified at 0.5, 4 and 24 hours. mRNA abundance profiles varied over time, with the highest level of activation occurring at earlier time points (0.5 and 4 hrs). In contrast to observations for other Leishmania species, most significantly changed mRNAs were up- rather than down-regulated, especially at early time points. Up-regulated transcripts over the first 24 hours belonged to pathways involving eicosanoid metabolism, oxidative stress, activation of PKC through G protein coupled receptors, or mechanism of gene regulation by peroxisome proliferators via PPARα. Additionally, a marked activation of Toll-receptor mediated pathways was observed. Comparison with published microarray data from macrophages infected with L. (Leishmania) chagasi indicate differences in the regulation of genes involved in signaling, motility and the immune response.ConclusionsResults show that the early (0.5 to 24 hours) human monocyte-derived macrophage response to L. (Viannia) panamensis is not quiescent, in contrast to published reports examining later response times (48–96 hours). Early macrophage responses are important for the developing cellular response at the site of infection. The kinetics and the mRNA abundance profiles induced by L. (Viannia) panamensis illustrate the dynamics of these interactions and the distinct biologic responses to different Leishmania species from the outset of infection within their primary host cell.
We have reported that attenuated Salmonella (S) carrying plasmids encoding the cysteine protease cruzipain (Cz) protects against Trypanosoma cruzi infection. Here, we determined whether immunoprotection could be improved by the oral coadministration of 3 Salmonella carrying the plasmids that encode the antigens Cz, Tc52, and Tc24. SCz+STc52+STc24-immunized mice presented an increased antibody response against each antigen compared with those in the single antigen-immunized groups, as well as higher trypomastigotes antibody-mediated lyses and cell invasion inhibition compared with controls. SCz+STc52+STc24-immunized and -challenged mice rendered lower parasitemia. Weight loss after infection was detected in all mice except those in the SCz+STc52+STc24 group. Moreover, cardiomyopathy-associated enzyme activity was significantly lower in SCz+STc24+STc52-immunized mice compared with controls. Few or no abnormalities were found in muscle tissues of SCz+STc24+STc52-immunized mice, whereas controls presented with inflammatory foci, necrosis, and amastigote nests. We conclude that a multicomponent approach that targets several invasion and metabolic mechanisms improves protection compared with single-component vaccines.
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