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

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-09-29T14:28:01Z No. of bitstreams: 1 Santos TA Role....pdf: 797145 bytes, checksum: f1a53c60daadd7bee2a4bf3a5e90fd71 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2014-09-29T14:28:11Z (GMT) No. of bitstreams: 1 Santos TA Role....pdf: 797145 bytes, checksum: f1a53c60daadd7bee2a4bf3a5e90fd71 (MD5)Made available in DSpace on 2014-09-29T16:39:00Z (GMT). No. of bitstreams: 1 Santos TA Role....pdf: 797145 bytes, checksum: f1a53c60daadd7bee2a4bf3a5e90fd71 (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil / University of Iowa and the Iowa City VA Medical Center. Iowa City, IowaUniversity of Iowa and the Iowa City VA Medical Center. Iowa City, IowaFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilUniversity of Iowa and the Iowa City VA Medical Center. Iowa City, IowaCentro de Investigaciones Biológicas, CSIC. Department of Chemical and Physical Biology. Madrid, SpainFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, BrasilUniversity of Iowa and the Iowa City VA Medical Center. Iowa City, IowaFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil / Institute for Investigation in Immunology, iii-INCT. National Institute of Science and Technology. São Paulo, SP, BrasilLipid 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

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