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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Leishmania braziliensis prostaglandin F-2 alpha synthase impacts host infection

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Autor(es):
Carneiro Alves-Ferreira, Eliza Vanessa [1] ; Ferreira, Tiago Rodrigues [1] ; Walrad, Pegine [2, 3] ; Kaye, Paul M. [2, 3] ; Cruz, Angela Kaysel [1]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell & Mol Biol, Ribeirao Preto - Brazil
[2] Univ York, Hull York Med Sch, York, N Yorkshire - England
[3] Univ York, Ctr Immunol & Infect, Dept Biol, York, N Yorkshire - England
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: PARASITES & VECTORS; v. 13, n. 1 JAN 8 2020.
Citações Web of Science: 0
Resumo

Background Prostaglandins (PG) are lipid mediators derived from arachidonic acid metabolism. They are involved in cellular processes such as inflammation and tissue homeostasis. PG production is not restricted to multicellular organisms. Trypanosomatids also synthesize several metabolites of arachidonic acid. Nevertheless, their biological role in these early-branching parasites and their role in host-parasite interaction are not well elucidated. Prostaglandin F-2 alpha synthase (PGF2S) has been observed in the Leishmania braziliensis secreted proteome and in L. donovani extracellular vesicles. Furthermore, we previously reported a positive correlation between L. braziliensis PGF2S (LbrPGF2S) expression and pathogenicity in mice. Methods LbrPGF2S gene expression and PGF2 alpha synthesis in promastigotes were detected and quantified by western blotting and EIA assay kit, respectively. To investigate LbrPGF2S localization in amastigotes during bone marrow-derived macrophage infection, parasites expressing mCherry-LbrPGF2S were generated and followed by time-lapse imaging for 48 h post-infection. PGF2S homolog sequences from Leishmania and humans were analyzed in silico using ClustalW on Geneious v6 and EMBOSS Needle. Results Leishmania braziliensis promastigotes synthesize prostaglandin F-2 alpha in the presence of arachidonic acid, with peak production in the stationary growth phase under heat stress. LbrPGF2S is a cytoplasmic protein enriched in the secretory site of the parasite cell body, the flagellar pocket. It is an enzyme constitutively expressed throughout promastigote development, but overexpression of LbrPGF2S leads to an increase of infectivity in vitro. The data suggest that LbrPGF2S may be released from intracellular amastigotes into the cytoplasm of bone marrow-derived macrophages over a 48-hour infection period, using time-lapse microscopy and mCherry-PGF2S (mChPGF2S)-expressing parasites. Conclusions LbrPGF2S, a parasite-derived protein, is targeted to the host cell cytoplasm. The putative transfer of this enzyme, involved in pro-inflammatory lipid mediator synthesis, to the host cell suggests a potential role in host-parasite interaction and may partially explain the increased pathogenicity associated with overexpression of LbrPGF2S in L. braziliensis. Our data provide valuable insights to help understand the importance of parasite-derived lipid mediators in pathogenesis. (AU)

Processo FAPESP: 13/50219-9 - Investigação sobre fatores e mecanismos do controle de expressão gênica em Leishmania: do papel de modificações pós-traducionais, RNAs não codificadores, cis-elementos e amplificação gênica
Beneficiário:Angela Kaysel Cruz
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 11/02040-4 - Investigação do papel da Prostaglandina F2-alfa sintase na interação entre Leishmania braziliensis e hospedeiro
Beneficiário:Eliza Vanessa Carneiro Alves Ferreira
Modalidade de apoio: Bolsas no Brasil - Doutorado
Processo FAPESP: 14/19400-1 - Estudo dos efeitos da metilação catalisada por PRMT7 na função e expressão da proteína ligante de RNA Alba20 em Leishmania major
Beneficiário:Tiago Rodrigues Ferreira
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 10/20597-3 - Investigação da interação parasito-hospedeiro: explorando modelos de estudo de virulência e tropismo
Beneficiário:Angela Kaysel Cruz
Modalidade de apoio: Auxílio à Pesquisa - Regular