title: Induction of autophagy correlates with increased parasite load of Leishmania amazonensis in BALB/c but not C57BL/6 macrophages.
abstract: We investigated the role of autophagy in infection of macrophages by Leishmania amazonensis. Induction of autophagy by IFN-gamma or starvation increased intracellular parasite load and the percentages of infected macrophages from BALB/c but not from C57BL/6 mice. In contrast, starvation did not affect the replication of either Leishmania major or Trypanosoma cruzi in BALB/c macrophages. In BALB/c macrophages, starvation resulted in increased monodansylcadaverine staining and in the appearance of double-membrane and myelin-like vesicles characteristic of autophagosomes. Increased parasite load was associated with a reduction in NO levels and was attenuated by wortmannin, an inhibitor of autophagy. In infected macrophages from BALB/c, but not from C57BL/6 mice, starvation increased the number of lipid bodies and the amounts of PGE(2) produced. Exogenous PGE(2) increased parasite load in macrophages from BALB/c, but not C57BL/6 mice. The cyclooxygenase inhibitor indomethacin prevented the increase of parasite load in starved BALB/c macrophages, and actually induced parasite killing. These results suggest that autophagy regulates the outcome of L. amazonensis infection in macrophages in a host strain specific manner.
authors.affiliation: Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro 21045-900, Brazil.
authors.forename: Roberta O
authors.initials: RO
authors.lastname: Pinheiro
authors.forename: Marise P
authors.initials: MP
authors.lastname: Nunes
authors.forename: Carla S
authors.initials: CS
authors.lastname: Pinheiro
authors.forename: Heloísa
authors.initials: H
authors.lastname: D'Avila
authors.forename: Patrícia T
authors.initials: PT
authors.lastname: Bozza
authors.forename: Christina M
authors.initials: CM
authors.lastname: Takiya
authors.forename: Suzana
authors.initials: S
authors.lastname: Côrte-Real
authors.forename: Célio G
authors.initials: CG
authors.lastname: Freire-de-Lima
authors.forename: George A
authors.initials: GA
authors.lastname: DosReis
mesh_terms: D000818:Animals; D001343:Autophagy; D005260:Female; D007894:Leishmania mexicana / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis; D011453:Prostaglandins / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000276:immunology
chemical_list: D011453:Prostaglandins; D009569:Nitric Oxide