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A novel receptor for platelet‐activating factor and lysophosphatidylcholine in Trypanosoma cruzi
Author(s) -
Coelho Felipe S.,
Oliveira Mauricio M.,
Vieira Danielle P.,
Torres Pedro H. M.,
Moreira Isabel C. F.,
MartinsDuarte Erica S.,
Gonçalves Inês C.,
Cabanelas Adriana,
Pascutti Pedro G.,
Fragoso Stenio P.,
Lopes Angela H.
Publication year - 2021
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.14778
Subject(s) - trypanosoma cruzi , biology , lysophosphatidylcholine , platelet activating factor , receptor , in vitro , microbiology and biotechnology , immunology , biochemistry , phospholipid , parasite hosting , membrane , phosphatidylcholine , world wide web , computer science
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.