Role of Prostaglandin F2α Production in Lipid Bodies From Leishmania infantum chagasi: Insights on Virulence

Abstract

Lipid bodies (LB; lipid droplets) are cytoplasmic organelles involved in lipid metabolism. Mammalian LBs display an important role in host-pathogen interactions, but the role of parasite LBs in biosynthesis of prostaglandin F2α (PGF2α) has not been investigated. We report herein that LBs increased in abundance during development of Leishmania infantum chagasi to a virulent metacyclic stage, as did the expression of PGF2α synthase (PGFS). The amount of parasite LBs and PGF2α were modulated by exogenous arachidonic acid. During macrophage infection, LBs were restricted to parasites inside the parasitophorous vacuoles (PV). We detected PGF2α receptor (FP) on the Leishmania PV surface. The blockage of FP with AL8810, a selective antagonist, hampered Leishmania infection, whereas the irreversible inhibition of cyclooxygenase with aspirin increased the parasite burden. These data demonstrate novel functions for parasite-derived LBs and PGF2α in the cellular metabolism of Leishmania and its evasion of the host immune response.

Resolvin D1 drives establishment of Leishmania amazonensis infection

“…The inhibition of enzymes from the lipid mediators pathways has been widely used to efficiently control inflammatory responses31 as well as Leishmania infection burden32. In our experimental model, we found that treatment with an inhibitor of 15-lypoxigenase resulted in a reduction of RvD1 production, which mirrored a decrease in intracellular parasite viability.…”

Crosstalk between purinergic receptors and lipid mediators in leishmaniasis

“…It is known that PGE 2 possesses anti-inflammatory activity, facilitating Leishmania infection in macrophages, suppressing inflammatory response in both cutaneous and visceral leishmaniasis [91–94]. Moreover, reinforcing the context of a beneficial effect of PGE 2 for Leishmania survival, it was demonstrated that several Leishmania species possess lipid corpuscles as organelles and L. infantum is able to produce and release PGs, such as PGF 2α itself [95, 96] (Fig. 1d).…”

Lipid droplet functions beyond energy storage

“…Inhibition of ATGL, genetically or pharmacologically, also impairs eicosanoid release in other types of immune cells, such as neutrophils [79]. In the intracellular parasites Leishmania and Trypanosoma , LDs can also act as a source of immunomodulatory prostaglandins implicated in improving the survival of the parasite within its host [80, 81]. The available evidence suggests that the enzymatically released AA is locally metabolized, as both eicosanoid precursors and eicosanoid producing enzymes have been found associated with LDs [75].…”