Abstract
Background Rhodnius prolixus is a blood-sucking bug vector of Trypanosoma cruzi and T. rangeli. T. cruzi is transmitted by vector feces deposited close to the wound produced by insect mouthparts, whereas T. rangeli invades salivary glands and is inoculated into the host skin. Bug saliva contains a set of nitric oxide-binding proteins, called nitrophorins, which deliver NO to host vessels and ensure vasodilation and blood feeding. NO is generated by nitric oxide synthases (NOS) present in the epithelium of bug salivary glands. Thus, T. rangeli is in close contact with NO while in the salivary glands.Methodology/Principal FindingsHere we show by immunohistochemical, biochemical and molecular techniques that inositolphosphate-containing glycolipids from trypanosomatids downregulate NO synthesis in the salivary glands of R. prolixus. Injecting insects with T. rangeli-derived glycoinositolphospholipids (Tr GIPL) or T. cruzi-derived glycoinositolphospholipids (Tc GIPL) specifically decreased NO production. Salivary gland treatment with Tc GIPL blocks NO production without greatly affecting NOS mRNA levels. NOS protein is virtually absent from either Tr GIPL- or Tc GIPL-treated salivary glands. Evaluation of NO synthesis by using a fluorescent NO probe showed that T. rangeli-infected or Tc GIPL-treated glands do not show extensive labeling. The same effect is readily obtained by treatment of salivary glands with the classical protein tyrosine phosphatase (PTP) inhibitor, sodium orthovanadate (SO). This suggests that parasite GIPLs induce the inhibition of a salivary gland PTP. GIPLs specifically suppressed NO production and did not affect other anti-hemostatic properties of saliva, such as the anti-clotting and anti-platelet activities.Conclusions/SignificanceTaken together, these data suggest that trypanosomatids have overcome NO generation using their surface GIPLs. Therefore, these molecules ensure parasite survival and may ultimately enhance parasite transmission.
Highlights
Invasion of vector salivary glands is a mandatory step in the life cycle of several pathogens
In order to verify the role of parasite infection in this nitric oxide (NO)-nitric oxide synthases (NOS) model, in the experiments we have separately evaluated the levels of NOS and NO synthesis in isolated salivary glands obtained from both control and T. rangeli-infected insects as shown on Figure 2
To test for the role of parasite-derived surface molecules in the suppression of NADPH-diaphorase activity we have evaluated the effect of T. cruzi-derived GIPLs, a GPI-anchored mucinlike glycoprotein isolated from epimastigote forms from T. cruzi surface glycoconjugate, GIPLs isolated from T. rangeli surface (Tr GIPL) and a GIPL preparation isolated from Phytomonas serpens, a trypanosomatid that infects plant [26,27,28]
Summary
Invasion of vector salivary glands is a mandatory step in the life cycle of several pathogens This event ensures pathogen transmission to a vertebrate host in the feeding cycle. By infecting the salivary glands, pathogens come into direct contact with vector saliva and with the anti-hemostatic factors it contains [1]. Their survival in this new environment relies on their ability to avoid the action of potentially harmful anti-hemostatic factors. This may be achieved by the manipulation of the production of some of these factors by parasite-derived molecules. T. rangeli is in close contact with NO while in the salivary glands
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