Induction of autophagy correlates with increased parasite load of Leishmania amazonensis in BALB/c but not C57BL/6 macrophages.
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.
Pinheiro
Roberta O
RO
Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro 21045-900, Brazil.
Nunes
Marise P
MP
Pinheiro
Carla S
CS
D'Avila
Heloísa
H
Bozza
Patrícia T
PT
Takiya
Christina M
CM
Côrte-Real
Suzana
S
Freire-de-Lima
Célio G
CG
DosReis
George A
GA
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
D011453:Prostaglandins; D009569:Nitric Oxide