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

被引:46
作者
Araujo-Santos, Theo [1 ,2 ,3 ]
Rodriguez, Nilda E. [2 ,3 ]
Moura-Pontes, Sara [1 ]
Dixt, Upasna Gaur [2 ,3 ]
Abanades, Daniel R. [4 ]
Bozza, Patricia T. [5 ]
Wilson, Mary E. [2 ,3 ]
Borges, Valeria Matos [1 ,6 ]
机构
[1] Oswaldo Cruz Fdn FIOCRUZ, Goncalo Moniz Res Ctr, Salvador, BA, Brazil
[2] Univ Iowa, Iowa City, IA USA
[3] Iowa City VA Med Ctr, Iowa City, IA USA
[4] CSIC, Ctr Invest Biol, Dept Chem & Phys Biol, Madrid, Spain
[5] Fundacao Oswaldo Cruz, Oswaldo Cruz Inst, Rio De Janeiro, Brazil
[6] III INCT Natl Inst Sci & Technol, Inst Invest Immunol, Sao Paulo, Brazil
基金
美国国家卫生研究院;
关键词
Leishmania infantum chagasi; lipid droplets; prostaglandin F-2 alpha; PGF(2 alpha) synthase; macrophage infection; MYCOBACTERIUM-LEPRAE; IN-VITRO; AMAZONENSIS INFECTION; INTRACELLULAR DOMAINS; EICOSANOID FORMATION; SCHWANN-CELLS; DROPLETS; PARASITE; MACROPHAGES; BACTERIAL;
D O I
10.1093/infdis/jiu299
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
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 F-2 alpha (PGF(2 alpha)) 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 PGF(2 alpha) synthase (PGFS). The amount of parasite LBs and PGF(2 alpha) were modulated by exogenous arachidonic acid. During macrophage infection, LBs were restricted to parasites inside the parasitophorous vacuoles (PV). We detected PGF(2 alpha) 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 PGF(2 alpha) in the cellular metabolism of Leishmania and its evasion of the host immune response.
引用
收藏
页码:1951 / 1961
页数:11
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