Lipid Bodies as Sites of Prostaglandin E2 Synthesis During Chagas Disease: Impact in the Parasite Escape Mechanism

Abstract

During Chagas disease, the Trypanosoma cruzi can induce some changes in the host cells in order to escape or manipulate the host immune response. The modulation of the lipid metabolism in the host phagocytes or in the parasite itself is one feature that has been observed. The goal of this mini review is to discuss the mechanisms that regulate intracellular lipid body (LB) biogenesis in the course of this parasite infection and their meaning to the pathophysiology of the disease. The interaction host–parasite induces LB (or lipid droplet) formation in a Toll-like receptor 2-dependent mechanism in macrophages and is enhanced by apoptotic cell uptake. Simultaneously, there is a lipid accumulation in the parasite due to the incorporation of host fatty acids. The increase in the LB accumulation during infection is correlated with an increase in the synthesis of PGE2 within the host cells and the parasite LBs. Moreover, the treatment with fatty acid synthase inhibitor C75 or non-steroidal anti-inflammatory drugs such as NS-398 and aspirin inhibited the LB biogenesis and also induced the down modulation of the eicosanoid production and the parasite replication. These findings show that LBs are organelles up modulated during the course of infection. Furthermore, the biogenesis of the LB is involved in the lipid mediator generation by both the macrophages and the parasite triggering escape mechanisms.

Lipid Droplet, a Key Player in Host-Parasite Interactions

“…Infected macrophages exhibit positive immunostaining for COX-2 and PGES, and both co-localize with PLIN2/ADRP staining, a LD structural protein, which confirms the presence of these enzymes inside LD in T. cruzi -infected macrophages. The association of PGE 2 production and parasite division highlighted the LD participation on evasion mechanisms of T. cruzi ( 30 , 167 ).…”

Lipid hijacking: A unifying theme in vector-borne diseases

“…During Leishmania infection, PGE 2 and prostaglandin F 2 α (PGF 2 α) were shown to be upregulated and enhance parasite viability ( Araújo-Santos et al, 2014 ; França-Costa et al, 2015 ; Alves-Ferreira et al, 2020 ). PGE 2 has an immunosuppressive effect during T. cruzi infection and can be derived from host or parasite LDs ( Toledo et al, 2016 ; Lovo-Martins et al, 2018 ; de Almeida et al, 2018 ). Although less understood, this eicosanoid may be somewhat involved in T. brucei immunosuppression as well.…”

Eosinophils and Neutrophils—Molecular Differences Revealed by Spontaneous Raman, CARS and Fluorescence Microscopy

“…The occurrence of LBs in leukocytes is associated with infection and inflammatory responses during which the increased size and number of LBs are considered as a marker of the leukocyte activation [ 22 , 23 ]. In principle, LBs are rapidly formed and secrete arachidonyl phopholipids used next in the production of eicosanoids, which are inflammatory mediators [ 24 , 25 , 26 ].…”