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- Title
Glycoinositolphospholipids from Trypanosomatids Subvert Nitric Oxide Production in Rhodnius prolixus Salivary Glands.
- Authors
Gazos-Lopes, Felipe; Mesquita, Rafael Dias; Silva-Cardoso, Lívia; Senna, Raquel; Silveira, Alan Barbosa; Jablonka, Willy; Cudischevitch, Cecília Oliveira; Carneiro, Alan Brito; Machado, Ednildo Alcantara; Lima, Luize G.; Monteiro, Robson Queiroz; Nussenzveig, Roberto Henrique; Folly, Evelize; Romeiro, Alexandre; Vanbeselaere, Jorick; Mendonça-Previato, Lucia; Previato, José Osvaldo; Valenzuela, Jesus G.; Chaves Ribeiro, José Marcos; Atella, Georgia Correa
- 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 Findings: Here 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 glycoinositolpho- spholipids (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/Significance: Taken 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.
- Subjects
RHODNIUS prolixus; TRYPANOSOMATIDAE; TRYPANOSOMA cruzi; TRYPANOSOMA rangeli; FECES; SALIVARY glands; NITRIC oxide
- Publication
PLoS ONE, 2012, Vol 7, Issue 10, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0047285