Role of prostaglandin F2α production in lipid bodies from Leishmania infantum chagasi: insights on virulence

前列腺素 F2α 的产生在利什曼原虫脂质体中的作用:对毒力的见解

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作者:Théo Araújo-Santos, Nilda E Rodríguez, Sara Moura-Pontes, Upasna Gaur Dixt, Daniel R Abánades, Patrícia T Bozza, Mary E Wilson, Valéria Matos Borges

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.

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