Induction of autophagy correlates with increased parasite load of Leishmania amazonensis in BALB/c but not C57BL/6 macrophages

• DOI: 10.1016/j.micinf.2008.11.006
• Publication Date: 2008-12-05T17:50:54Z
• Authors: Roberta O. Pinheiro; Marise P. Nunes; Carla S. Pinheiro; Heloísa D'Avila; Patrícia T. Bozza; Christina M. Takiya; Suzana Côrte-Real; Célio G. Freire-d...; George A. DosReis
• Keywords: Male; 2. Zero hunger; Mice, Inbred BALB C; 0303 health sciences; Macrophages; Trypanosoma cruzi; Leishmania mexicana; Nitric Oxide; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Autophagy; Prostaglandins; Animals; Female

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.