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


RESULTS
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.


CONCLUSIONS
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.
Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Felipe
F
Gazos-Lopes
Rafael Dias
RD
Mesquita
Lívia
L
Silva-Cardoso
Raquel
R
Senna
Alan Barbosa
AB
Silveira
Willy
W
Jablonka
Cecília Oliveira
CO
Cudischevitch
Alan Brito
AB
Carneiro
Ednildo Alcantara
EA
Machado
Luize G
LG
Lima
Robson Queiroz
RQ
Monteiro
Roberto Henrique
RH
Nussenzveig
Evelize
E
Folly
Alexandre
A
Romeiro
Jorick
J
Vanbeselaere
Lucia
L
Mendonça-Previato
José Osvaldo
JO
Previato
Jesus G
JG
Valenzuela
José Marcos Chaves
JM
Ribeiro
Georgia Correa
GC
Atella
Mário Alberto Cardoso
MA
Silva-Neto
D000818:Animals; D014355:Chagas Disease / Q000378:metabolism / Q000469:parasitology / Q000635:transmission*; D006017:Glycolipids / Q000378:metabolism*; D006790:Host-Parasite Interactions; D007303:Insect Vectors / Q000378:metabolism / Q000469:parasitology; D009569:Nitric Oxide / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012239:Rhodnius / Q000378:metabolism* / Q000469:parasitology; D012469:Salivary Glands / Q000187:drug effects / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000378:metabolism* / Q000472:pathogenicity; D057509:Trypanosoma rangeli / Q000378:metabolism* / Q000472:pathogenicity; D014638:Vanadates / Q000494:pharmacology
D006017:Glycolipids; D009569:Nitric Oxide; D014638:Vanadates; D052248:Nitric Oxide Synthase Type I; D017027:Protein Tyrosine Phosphatases