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

Abstract

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.

PAF‐induced inflammatory and immuno‐allergic ophthalmic diseases and their mitigation with PAF receptor antagonists: Cell and nuclear effects

“…Lastly, there has been a debate about whether all effects of PAF described in various cells, tissues and organs described above are mediated via its cell‐membrane‐bound receptors and on the relative roles of cell‐surface and nuclear‐membrane‐bound PAF receptors 127–129 . Based on the schematic in Figure 3, it would appear that both sets of receptors are involved in many if not all physiological and pathological actions of PAF.…”

“…Lastly, there has been a debate about whether all effects of PAF described in various cells, tissues and organs described above are mediated via its cell‐membrane‐bound receptors and on the relative roles of cell‐surface and nuclear‐membrane‐bound PAF receptors. 127 , 128 , 129 Based on the schematic in Figure 3 , it would appear that both sets of receptors are involved in many if not all physiological and pathological actions of PAF. It could be that the acute transmitter/mediator and physiological effects recruit only the outer cell‐membrane‐bound PAF receptors, whereas the nuclear receptors are involved in chronic and pathological conditions but also require the cell‐membrane‐bound PAF receptors.…”

Análise genômica comparativa e evolutiva do genoma do monoxeno Blechomonas sp. TCC303E

“…Os grupos que contribuem nos processos de infecção são os grupos OG0000115 e OG0000116. O primeiro é composto por proteínas homólogas à família de receptores de progestina e adiponectina (PAQRs: the progestin and adiponectin family of receptors) que em T. cruzi há evidências da sua funcionalidade e que desencadeia a diferenciação celular, contribuindo para o processo de infecção a macrófagos (Coelho et al 2021). O segundo grupo é formado por proteínas ecotin-like, um inibidor de serina protease, considerado em diversos patógenos como fator de virulência, incluindo nos gêneros Trypanosoma e Leishmania, embora não totalmente esclarecido.…”