Abstract
Background Trypanosoma cruzi is the etiological agent of Chagas' disease. Cysteine peptidases are relevant to several aspects of the T. cruzi life cycle and are implicated in parasite-mammalian host relationships. However, little is known about the factors that contribute to the parasite-insect host interaction.Methodology/Principal FindingsHere, we have investigated whether cruzipain could be involved in the interaction of T. cruzi with the invertebrate host. We analyzed the effect of treatment of T. cruzi epimastigotes with anti-cruzipain antibodies or with a panel of cysteine peptidase inhibitors (cystatin, antipain, E-64, leupeptin, iodocetamide or CA-074-OMe) on parasite adhesion to Rhodnius prolixus posterior midgut ex vivo. All treatments, with the exception of CA074-OMe, significantly decreased parasite adhesion to R. prolixus midgut. Cystatin presented a dose-dependent reduction on the adhesion. Comparison of the adhesion rate among several T. cruzi isolates revealed that the G isolate, which naturally possesses low levels of active cruzipain, adhered to a lesser extent in comparison to Dm28c, Y and CL Brener isolates. Transgenic epimastigotes overexpressing an endogenous cruzipain inhibitor (pCHAG), chagasin, and that have reduced levels of active cruzipain adhered to the insect gut 73% less than the wild-type parasites. The adhesion of pCHAG parasites was partially restored by the addition of exogenous cruzipain. In vivo colonization experiments revealed low levels of pCHAG parasites in comparison to wild-type. Parasites isolated after passage in the insect presented a drastic enhancement in the expression of surface cruzipain.Conclusions/SignificanceThese data highlight, for the first time, that cruzipain contributes to the interaction of T. cruzi with the insect host.
Highlights
Chagas’ disease remains one of the most important neglected diseases of Latin America, and it has become a world health problem due to migration of infected people from endemic countries [1]
Chagas’ disease, a neglected tropical disease caused by Trypanosoma cruzi, is transmitted to vertebrate hosts by hematophagous insects
Cruzipain is a lysosomal cysteine peptidase, which plays an important role in parasite infectivity, intracellular growth and differentiation, and is abundantly expressed on the surface of epimastigotes. Since these forms face the insect vector environment during the life cycle, it is conceivable that cruzipain may participate in the interaction process with the invertebrate host
Summary
Chagas’ disease remains one of the most important neglected diseases of Latin America, and it has become a world health problem due to migration of infected people from endemic countries [1]. The etiological agent Trypanosoma cruzi is transmitted in nature to vertebrate hosts through hematophagous insects from the Reduviidae family. During their development within insects, the parasites undergo profound morphological changes, modulating surface molecules to enable interactions with specific insect tissues that are essential for their survival, development and successful transmission to the vertebrate host. T. cruzi-insect vector interaction begins when the insect feeds on blood of an infected vertebrate host. In the rectum, where the highest parasite population occurs, a proportion of epimastigotes attach to the rectal cuticle by hydrophobic interactions and transforms into non-replicative metacyclic trypomastigotes (metacyclogenesis), which are eliminated with the feces and urine during blood feeding, infecting another mammalian host. Little is known about the factors that contribute to the parasite-insect host interaction
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