title: Host cell lipid bodies triggered by Trypanosoma cruzi infection and enhanced by the uptake of apoptotic cells are associated with prostaglandin E₂ generation and increased parasite growth.
abstract: Lipid bodies (lipid droplets) are lipid-rich organelles with functions in cell metabolism and signaling. Here, we investigate the mechanisms of Trypanosoma cruzi-induced lipid body formation and their contributions to host-parasite interplay. We demonstrate that T. cruzi-induced lipid body formation in macrophages occurs in a Toll-like receptor 2-dependent mechanism and is potentiated by apoptotic cell uptake. Lipid body biogenesis and prostaglandin E₂ (PGE₂) production triggered by apoptotic cell uptake was largely dependent of α(v)β₃ and transforming growth factor-β signaling. T. cruzi-induced lipid bodies act as sites of increased PGE synthesis. Inhibition of lipid body biogenesis by the fatty acid synthase inhibitor C75 reversed the effects of apoptotic cells on lipid body formation, eicosanoid synthesis, and parasite replication. Our findings indicate that lipid bodies are highly regulated organelles during T. cruzi infection with roles in lipid mediator generation by macrophages and are potentially involved in T. cruzi-triggered escape mechanisms.
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Heloisa
authors.initials: H
authors.lastname: D'Avila
authors.forename: Célio G
authors.initials: CG
authors.lastname: Freire-de-Lima
authors.forename: Natalia R
authors.initials: NR
authors.lastname: Roque
authors.forename: Livia
authors.initials: L
authors.lastname: Teixeira
authors.forename: Christina
authors.initials: C
authors.lastname: Barja-Fidalgo
authors.forename: Adriana R
authors.initials: AR
authors.lastname: Silva
authors.forename: Rossana C N
authors.initials: RC
authors.lastname: Melo
authors.forename: George A
authors.initials: GA
authors.lastname: Dosreis
authors.forename: Hugo C
authors.initials: HC
authors.lastname: Castro-Faria-Neto
authors.forename: Patrícia T
authors.initials: PT
authors.lastname: Bozza
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000473:pathology*; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006790:Host-Parasite Interactions; D050356:Lipid Metabolism; D008264:Macrophages / Q000378:metabolism* / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000254:growth & development / Q000472:pathogenicity*
chemical_list: D051195:Toll-Like Receptor 2; D015232:Dinoprostone