Here, There, and Everywhere: The Ubiquitous Distribution of the Immunosignaling Molecule Lysophosphatidylcholine and Its Role on Chagas Disease

Abstract

Chagas disease is a severe illness, which can lead to death if the patients are not promptly treated. The disease is caused by the protozoan parasite Trypanosoma cruzi, which is mostly transmitted by a triatomine insect vector. There are 8–10 million people infected with T. cruzi in the world, but the transmission of such disease by bugs occurs only in the Americas, especially Latin America. Chronically infected patients will develop cardiac diseases (30%) and up digestive, neurological, or mixed disorders (10%). Lysophosphatidylcholine (LPC) is the major phospholipid component of oxidized low-density lipoproteins associated with atherosclerosis-related tissue damage. Insect-derived LPC powerfully attracts inflammatory cells to the site of the insect bite, enhances parasite invasion, and inhibits the production of nitric oxide by T. cruzi-stimulated macrophages. The recognition of the ubiquitous presence of LPC on the vector saliva, its production by the parasite itself and its presence both on patient plasma and its role on diverse host × parasite interaction systems lead us to compare its distribution in nature with the title of the famous Beatles song “Here, There and Everywhere” recorded exactly 50 years ago in 1966. Here, we review the major findings pointing out the role of such molecule as an immunosignaling modulator of Chagas disease transmission. Also, we believe that future investigation of the connection of this ubiquity and the immune role of such molecule may lead in the future to novel methods to control parasite transmission, infection, and pathogenesis.

Mapping of host-parasite-microbiome interactions reveals metabolic determinants of tropism and tolerance in Chagas disease

“…2 and data file S1). Lysophosphatidylcholines (LPCs), in particular, increase T. cruzi invasion and inflammatory cell recruitment while inhibiting antiparasitic nitric oxide production ( 8 ). Thus, the sustained PC elevation observed in the esophagus and large intestine may contribute to CD progression in those organs.…”

Ginseng-Induced Changes to Blood Vessel Dilation and the Metabolome of Rats

“…LPC, a major phospholipid of oxLDL that is closely related with the tissue damage caused by atherosclerosis [18,19] is generally produced under various physiological conditions by endogenous…”

“…LPC, a major phospholipid of oxLDL that is closely related with the tissue damage caused by atherosclerosis [18,19] is generally produced under various physiological conditions by endogenous LP-PLA 2 and LCAT-mediated hydrolysis of lipoproteins [19]. LPCs play numerous important physiological and pathophysiological roles, including in vascular development, reproduction, and myelination, along with associations with neuronal diseases and cancer, in both humans and animals.…”

Lipids From Trypanosoma cruzi Amastigotes of RA and K98 Strains Generate a Pro-inflammatory Response via TLR2/6

“…Lysophospholipids, mediators in the synthetic pathways of various phospholipids and structural components, can also act as signaling molecules (Sowinska et al, 2016 ). A growing body of evidence suggests that LPC plays a role in the regulation of cell immune responses and chronic diseases progression (Matsumoto et al, 2007 ; Silva-Neto et al, 2016 ). Besides, it has been proposed that LPC is a dual activity molecule, able to trigger a classical pro-inflammatory phenotype as well as to induce an anti-inflammatory phenotype in macrophages (Carneiro et al, 2013 ; Assunção et al, 2017 ).…”