The role of parasite persistence in pathogenesis of Chagas heart disease.

Chagas disease (CD) is caused by the infection with the protozoan haemoflagellate Trypanosoma cruzi. This disease is still a great menace to public health, and is largely neglected as it affects mostly the poorest populations of Latin America. Nonetheless, there are neither effective diagnostic markers nor therapeutic options to accurately detect and efficiently cure this chronic infection. In spite of the great advances in the knowledge of the biology of natural transmission, as well as the immunobiology of the host-parasite interaction, the understanding of the pathogenesis of CD remains largely elusive. In the recent decades, a controversy in the research community has developed about the relevance of parasite persistence or autoimmune phenomena in the development of chronic cardiac pathology. One of the most notable aspects of chronic CD is the progressive deterioration of cardiac function, derived mostly from structural derangement, as a consequence of the intense inflammatory process. Here we review the evidence supporting the multifactorial nature of Chagas heart disease comprising pathogen persistence and altered host immunoregulatory mechanisms.

Impairment of Interleukin-17A Expression in Canine Visceral Leishmaniosis is Correlated with Reduced Interferon-γ and Inducible Nitric Oxide Synthase Expression.

Dogs are the primary urban reservoir of Leishmania infantum and play a crucial role in the transmission of this parasite to man via sandflies. The spleen and liver are the main target organs of L. infantum infection, but few studies have evaluated the immune response to this infection in the canine liver. To identify the immunological mediators involved in resistance and/or susceptibility to canine visceral leishmaniosis (CVL), we selected 21 dogs naturally infected by L. infantum and classified as asymptomatic or symptomatic. Immunological parameters were analysed and correlations with clinical signs were determined. Symptomatic dogs showed higher numbers of parasites and less leucocyte infiltration in the liver compared with asymptomatic dogs. The progression of this disease was characterized not only by the down regulation of T helper (Th) 1-related cytokines, such as interferon (IFN)-γ and tumour necrosis factor (TNF)-α, but also by the down regulation of genes encoding interleukin (IL)-17A, inducible nitric oxide synthase (iNOS) and IL-10 in the spleen and liver in symptomatic dogs compared with asymptomatic dogs. Importantly, IL-17A gene transcription level was positively correlated with mRNA expression for iNOS and IFN-γ. Th1- and Th17-related cytokines therefore appear to play a role in restricting parasite growth via iNOS activation and decrease susceptibility of dogs to CVL.

Schistosomicidal and trypanocidal structure-activity relationships for (±)-licarin A and its (-)- and (+)-enantiomers.

(±)-Licarin A (1) was obtained by oxidative coupling, and its enantiomers, (-)-licarin A (2) and (+)-licarin A (3), were resolved by chiral HPLC. Schistosomicidal and trypanocidal activities of these compounds were evaluated in vitro against Schistosoma mansoni adult worms and trypomastigote forms of Trypanosoma cruzi. The racemic mixture (1) displayed significant schistosomicidal activity with an LC50 value of 53.57 µM and moderate trypanocidal activity with an IC50 value of 127.17 µM. On the other hand, the (-)-enantiomer (2), displaying a LC50 value of 91.71 µM, was more active against S. mansoni than the (+)-enantiomer (3), which did not show activity. For the trypanocidal assay, enantiomer 2 showed more significant activity (IC50 of 23.46 µM) than enantiomer 3, which showed an IC50 value of 87.73 µM. Therefore, these results suggest that (±)-licarin A (1) and (-)-licarin A (2) are promising compounds that could be used for the development of schistosomicidal and trypanocidal agents.