Glycoinositolphospholipids from Trypanosomatids subvert nitric oxide production in Rhodnius prolixus salivary glands

• Published in: PloS one Vol. 7; no. 10; p. e47285
• Main 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, Ribeiro, José Marcos Chaves, Atella, Georgia Correa, Silva-Neto, Mário Alberto Cardoso
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15-10-2012; Public Library of Science (PLoS)
• Subjects: Animals; Binding proteins; Biology; Blood; Blood vessels; Chagas Disease - metabolism; Chagas Disease - parasitology; Chagas Disease - transmission; Chemical synthesis; Clotting; Disease transmission; Enzymes; Epithelium; Fluorescence; Gene expression; Glands; Glycolipids; Glycolipids - metabolism; Health aspects; Host-Parasite Interactions; Infections; Infectious diseases; Insect Vectors - metabolism; Insect Vectors - parasitology; Insects; Laboratories; Messenger RNA; Molecular biology; Mouthparts; mRNA; Nitric oxide; Nitric Oxide - biosynthesis; Nitric Oxide Synthase Type I - antagonists & inhibitors; Nitric Oxide Synthase Type I - metabolism; Nitric-oxide synthase; Orthovanadate; Parasites; Pathogens; Phosphatase; Protein Tyrosine Phosphatases - antagonists & inhibitors; Protein Tyrosine Phosphatases - metabolism; Protein-tyrosine-phosphatase; Proteins; Rhodnius - metabolism; Rhodnius - parasitology; Rhodnius prolixus; Saliva; Salivary gland; Salivary glands; Salivary Glands - drug effects; Salivary Glands - metabolism; Skin; Sodium; Sodium orthovanadate; Trypanosoma cruzi; Trypanosoma cruzi - metabolism; Trypanosoma cruzi - pathogenicity; Trypanosoma rangeli; Trypanosoma rangeli - metabolism; Trypanosoma rangeli - pathogenicity; Tyrosine; Vanadates - pharmacology; Vasodilation; Wounds; Brazil; Rio de Janeiro Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0047285

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.
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 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.
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.