Role of prostaglandin F2α production in lipid bodies from Leishmania infantum chagasi: insights on virulence.
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.
Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (FIOCRUZ) Federal University of Bahia (UFBA), Salvador, Bahia, Brazil University of Iowa and the Iowa City VA Medical Center, Iowa.
Théo
T
Araújo-Santos
University of Iowa and the Iowa City VA Medical Center, Iowa.
Nilda E
NE
Rodríguez
Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (FIOCRUZ) Federal University of Bahia (UFBA), Salvador, Bahia, Brazil.
Sara
S
Moura-Pontes
University of Iowa and the Iowa City VA Medical Center, Iowa.
Upasna Gaur
UG
Dixt
Department of Chemical and Physical Biology, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain.
Daniel R
DR
Abánades
Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro.
Patrícia T
PT
Bozza
University of Iowa and the Iowa City VA Medical Center, Iowa.
Mary E
ME
Wilson
Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (FIOCRUZ) Federal University of Bahia (UFBA), Salvador, Bahia, Brazil Institute for Investigation in Immunology, iii-INCT (National Institute of Science and Technology), São Paulo, Brazil.
Valéria Matos
VM
Borges
D000818:Animals; D015237:Dinoprost / Q000378:metabolism*; D018314:Leishmania infantum / Q000254:growth & development* / Q000378:metabolism*; D066292:Lipid Droplets / Q000378:metabolism*; D008264:Macrophages / Q000469:parasitology*; D008297:Male; D008647:Mesocricetus; D008807:Mice, Inbred BALB C; D059208:Parasite Load
D015237:Dinoprost
Leishmania infantum chagasi; PGF2α synthase; lipid droplets; macrophage infection; prostaglandin F2α