Lipid Body Organelles within the Parasite Trypanosoma cruzi: A Role for Intracellular Arachidonic Acid Metabolism

• Published in: PloS one 2016-08, Vol.11 (8), p.e0160433
• Main Authors: Toledo, Daniel A M, Roque, Natália R, Teixeira, Lívia, Milán-Garcés, Erix A, Carneiro, Alan B, Almeida, Mariana R, Andrade, Gustavo F S, Martins, Jefferson S, Pinho, Roberto R, Freire-de-Lima, Célio G, Bozza, Patrícia T, D'Avila, Heloisa, Melo, Rossana C N
• Format: Article
• Language: English
• Subjects: Acids; Adaptive immunity; Amastigotes; Animals; Arachidonic acid; Arachidonic Acid - metabolism; Biology and Life Sciences; Biosynthesis; Brugia malayi; Causes of; Cellular biology; Chagas Disease - metabolism; Chemistry; Development and progression; Dinoprostone - metabolism; Eicosanoids; Electron density; Electron microscopy; Eukaryotes; Fatty acids; Genetic aspects; Immunity; Immunomodulation; Inclusions; Infections; Infectious diseases; Inflammation; Intracellular; Laboratories; Light microscopy; Lipid bodies; Lipid Droplets - metabolism; Lipid Droplets - ultrastructure; Lipids; Macrophages; Mammalian cells; Mass spectroscopy; Medicine and Health Sciences; Metabolism; Microscopy; Organelles; Parasites; Pathogens; Physiological aspects; Prostaglandin E2; Prostaglandin-E Synthases - biosynthesis; Protozoa; Protozoan Proteins - biosynthesis; Raman spectroscopy; Spectroscopy; Toxoplasma gondii; Transmission electron microscopy; Trends; Triglycerides; Trypanosoma cruzi; Trypanosoma cruzi - metabolism; Trypanosoma cruzi - ultrastructure; Trypanosomiasis; Trypomastigotes; Vector-borne diseases
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0160433

Most eukaryotic cells contain varying amounts of cytosolic lipidic inclusions termed lipid bodies (LBs) or lipid droplets (LDs). In mammalian cells, such as macrophages, these lipid-rich organelles are formed in response to host-pathogen interaction during infectious diseases and are sites for biosynthesis of arachidonic acid (AA)-derived inflammatory mediators (eicosanoids). Less clear are the functions of LBs in pathogenic lower eukaryotes. In this study, we demonstrated that LBs, visualized by light microscopy with different probes and transmission electron microscopy (TEM), are produced in trypomastigote forms of the parasite Trypanosoma cruzi, the causal agent of Chagas' disease, after both host interaction and exogenous AA stimulation. Quantitative TEM revealed that LBs from amastigotes, the intracellular forms of the parasite, growing in vivo have increased size and electron-density compared to LBs from amastigotes living in vitro. AA-stimulated trypomastigotes released high amounts of prostaglandin E2 (PGE2) and showed PGE2 synthase expression. Raman spectroscopy demonstrated increased unsaturated lipid content and AA incorporation in stimulated parasites. Moreover, both Raman and MALDI mass spectroscopy revealed increased AA content in LBs purified from AA-stimulated parasites compared to LBs from unstimulated group. By using a specific technique for eicosanoid detection, we immunolocalized PGE2 within LBs from AA-stimulated trypomastigotes. Altogether, our findings demonstrate that LBs from the parasite Trypanosoma cruzi are not just lipid storage inclusions but dynamic organelles, able to respond to host interaction and inflammatory events and involved in the AA metabolism. Acting as sources of PGE2, a potent immunomodulatory lipid mediator that inhibits many aspects of innate and adaptive immunity, newly-formed parasite LBs may be implicated with the pathogen survival in its host.