Table 3.
Role of ROS in Protozoan Infections of Medical Importance
Pathogen | Observed effects of ROS/antioxidants on pathogen's burden | Model | Associated mechanisms of resistance | Suspected mechanisms underlying results | References |
---|---|---|---|---|---|
Leishmania major | NAC treatment of BALB/c mice reduced burden, whereas BSO (a drug that depletes gluthatione) increased burden in C57BL/6 footpads | Mice were treated with NAC | Increase in the frequency of IFN-γ-secreting lymphocytes in draining popliteal lymph nodes from NAC-treated mice | It remains unknown whether reduction of burden is dependent on IFN-γ-secreting lymphocytes | (56, 270, 276) |
Treatment of infected macrophages with GSH-depleting BSO before IFN-γ/LPS activation increased burden | Elicited peritoneal macrophages(C57BL/6 mice) treated with BSO for 24 h, activated with IFN-γ/LPS | GSH depletion was associated with a decrease in NO production | It remains unknown whether GSH inhibited L. major growth in macrophages | (276) | |
NRF2-activator resveratrol reduced parasite burden of infected macrophages | Elicited peritoneal macrophages or J774 murine cell line treated with resveratrol | Resveratrol acts to reduce parasite burden in macrophages at lower doses than directly | The mechanisms activated by resveratrol remain unknown | (138) | |
Leishmania amazonensis | NAC treatment reduced parasite burden in footpads from infected BALB/c mice | NAC treatment of BALB/c mice | No clues to how NAC reduced footpad parasite burden | No suspected mechanism | (205) |
DETC, an inhibitor of SOD activity, promoted parasite destruction in infected macrophages or reduced parasite burden in vivo, NAC reversed this effect | Peritoneal macrophages from BALB/c mice | Superoxide production seems to be a killing mechanism. No controls treated only with NAC | IFN β increases parasite burden through induction of SOD and decrease of superoxide | (141) | |
Trypanosoma cruzi | ROS exposure of epimastigotes increased their growth | Epimastigotes grow more actively in LIT medium containing H2O2 | ROS affects cell signaling. | No similar mechanisms are known in amastigotes | (77, 226) |
Increased infection under oxidative conditions and vice versa, in macrophages and in vivo. Burden reduced in infected macrophages incubated with antioxidants, transfected with Nrf2 or HO-1, and vice versa in H2O2 or PMA. Treatment with NRF2-activators reduce parasitemia, also reduced in gp91phox−/−.mice | Elicited peritoneal macrophages, BMMs or THP-1 cells; C57BL/6 and NOX2(gp91phox)−/− mice | Reduction of labile iron pool associated with reduction in parasite growth by antioxidants. NO, type I IFN, and apoptosis of infected cells not involved | Direct effects of ROS on amastigote proliferation were not ruled out, nor were mechanisms indirectly associated with reduction of labile iron pool | (93, 210, 218, 235, 272, 285) |
BSO, buthionine sulfoximine; LPS, lipopolysaccharide; NO, nitric oxide; SOD, superoxide dismutase.