Effects of platelet-activating factor on the interaction of Trypanosoma cruzi with Rhodnius prolixus

Zimmermann, Luciana Teixeira; Folly, Evelize; Gomes, M. Teixeira; Alviano, Daniela Sales; Alviano, Celuta Sales; Silva-Filho, F. C.; Atella, Geórgia C.; Lopes, Angela H.

doi:10.1007/s00436-010-2194-2

Cited by 4 publications

(3 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…LPC, TXA2, and PAF are lipid mediators that share a common chemical structure, biosynthetic pathways [98] and the ability to activate platelets [99]–[101]. Previous results from our group have shown that PAF-treated T. cruzi is far more infective towards both mouse macrophages [14] and the insect vector R. prolixus [102]. TXA2 synthesized by T. cruzi controls the proliferation of the parasite and resulting inflammatory response to infection in the mouse [12].…”

Section: Discussionmentioning

confidence: 99%

Structural and Functional Analysis of a Platelet-Activating Lysophosphatidylcholine of Trypanosoma cruzi

et al. 2014

Self Cite

View full text Add to dashboard Cite

Background Trypanosoma cruzi is the causative agent of the life-threatening Chagas disease, in which increased platelet aggregation related to myocarditis is observed. Platelet-activating factor (PAF) is a potent intercellular lipid mediator and second messenger that exerts its activity through a PAF-specific receptor (PAFR). Previous data from our group suggested that T. cruzi synthesizes a phospholipid with PAF-like activity. The structure of T. cruzi PAF-like molecule, however, remains elusive.Methodology/Principal findingsHere, we have purified and structurally characterized the putative T. cruzi PAF-like molecule by electrospray ionization-tandem mass spectrometry (ESI-MS/MS). Our ESI-MS/MS data demonstrated that the T. cruzi PAF-like molecule is actually a lysophosphatidylcholine (LPC), namely sn-1 C18:1(delta 9)-LPC. Similar to PAF, the platelet-aggregating activity of C18:1-LPC was abrogated by the PAFR antagonist, WEB 2086. Other major LPC species, i.e., C16:0-, C18:0-, and C18:2-LPC, were also characterized in all T. cruzi stages. These LPC species, however, failed to induce platelet aggregation. Quantification of T. cruzi LPC species by ESI-MS revealed that intracellular amastigote and trypomastigote forms have much higher levels of C18:1-LPC than epimastigote and metacyclic trypomastigote forms. C18:1-LPC was also found to be secreted by the parasite in extracellular vesicles (EV) and an EV-free fraction. A three-dimensional model of PAFR was constructed and a molecular docking study was performed to predict the interactions between the PAFR model and PAF, and each LPC species. Molecular docking data suggested that, contrary to other LPC species analyzed, C18:1-LPC is predicted to interact with the PAFR model in a fashion similar to PAF.Conclusions/SignificanceTaken together, our data indicate that T. cruzi synthesizes a bioactive C18:1-LPC, which aggregates platelets via PAFR. We propose that C18:1-LPC might be an important lipid mediator in the progression of Chagas disease and its biosynthesis could eventually be exploited as a potential target for new therapeutic interventions.

show abstract

Section: Discussionmentioning

confidence: 99%

Structural and Functional Analysis of a Platelet-Activating Lysophosphatidylcholine of Trypanosoma cruzi

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…In this context, studies analysing the relationship between T. cruzi and its vector, triatomines (Hemíptera: Reduviidae: Triatominae), have been emphasized in recent years (Zimmermann et al . 2010; Garcia et al 2010; Ennes-Vidal et al . 2011).…”

Section: Discussionmentioning

confidence: 99%

Trypanosoma cruziheparin-binding proteins mediate the adherence of epimastigotes to the midgut epithelial cells ofRhodnius prolixus

et al. 2012

View full text Add to dashboard Cite

Heparin-binding proteins (HBPs) have been demonstrated in both infective forms of Trypanosoma cruzi and are involved in the recognition and invasion of mammalian cells. In this study, we evaluated the potential biological function of these proteins during the parasite-vector interaction. HBPs, with molecular masses of 65·8 kDa and 59 kDa, were isolated from epimastigotes by heparin affinity chromatography and identified by biotin-conjugated sulfated glycosaminoglycans (GAGs). Surface plasmon resonance biosensor analysis demonstrated stable receptor-ligand binding based on the association and dissociation values. Pre-incubation of epimastigotes with GAGs led to an inhibition of parasite binding to immobilized heparin. Competition assays were performed to evaluate the role of the HBP-GAG interaction in the recognition and adhesion of epimastigotes to midgut epithelial cells of Rhodnius prolixus. Epithelial cells pre-incubated with HBPs yielded a 3·8-fold inhibition in the adhesion of epimastigotes. The pre-treatment of epimastigotes with heparin, heparan sulfate and chondroitin sulfate significantly inhibited parasite adhesion to midgut epithelial cells, which was confirmed by scanning electron microscopy. We provide evidence that heparin-binding proteins are found on the surface of T. cruzi epimastigotes and demonstrate their key role in the recognition of sulfated GAGs on the surface of midgut epithelial cells of the insect vector.

show abstract

“…A similar phenomenon has already been reported in Leishmania amazonensis , as PAF increased L. amazonensis invasion in mouse macrophages, which was inhibited by WEB 2086 (Rosa et al., 2002). Likewise, the interaction between T. cruzi and one of its insect vectors, Rhodnius prolixus , was abolished when the parasites were pretreated with WEB 2086 (Zimmermann et al, 2011). Also, the interactions between WT and KO control parasites and macrophages were no different.…”

Section: Discussionmentioning

confidence: 99%

A novel receptor for platelet‐activating factor and lysophosphatidylcholine in Trypanosoma cruzi

Coelho

Oliveira

Vieira

et al. 2021

Molecular Microbiology

Self Cite

View full text Add to dashboard Cite

The lipid mediators, platelet‐activating factor (PAF) and lysophosphatidylcholine (LPC), play relevant pathophysiological roles in Trypanosoma cruzi infection. Several species of LPC, including C18:1 LPC, which mimics the effects of PAF, are synthesized by T. cruzi. The present study identified a receptor in T. cruzi, which was predicted to bind to PAF, and found it to be homologous to members of the progestin and adiponectin family of receptors (PAQRs). We constructed a three‐dimensional model of the T. cruzi PAQR (TcPAQR) and performed molecular docking to predict the interactions of the TcPAQR model with C16:0 PAF and C18:1 LPC. We knocked out T. cruzi PAQR (TcPAQR) gene and confirmed the identity of the expressed protein through immunoblotting and immunofluorescence assays using an anti‐human PAQR antibody. Wild‐type and knockout (KO) parasites were also used to investigate the in vitro cell differentiation and interactions with peritoneal mouse macrophages; TcPAQR KO parasites were unable to react to C16:0 PAF or C18:1 LPC. Our data are highly suggestive that PAF and LPC act through TcPAQR in T. cruzi, triggering its cellular differentiation and ability to infect macrophages.

show abstract

Effects of platelet-activating factor on the interaction of Trypanosoma cruzi with Rhodnius prolixus

Cited by 4 publications

References 42 publications

Structural and Functional Analysis of a Platelet-Activating Lysophosphatidylcholine of Trypanosoma cruzi

Structural and Functional Analysis of a Platelet-Activating Lysophosphatidylcholine of Trypanosoma cruzi

Trypanosoma cruziheparin-binding proteins mediate the adherence of epimastigotes to the midgut epithelial cells ofRhodnius prolixus

A novel receptor for platelet‐activating factor and lysophosphatidylcholine in Trypanosoma cruzi

Contact Info

Product

Resources

About