Fig 1.
The outcome of HO-1 expression depends on the stage of the disease. In the liver stage, HO-1 protects infected hepatocytes from dying, allowing a greater parasitism, thus reducing disease resistance to infection. During erythrocytic phase, HO-1 is crucial to prevent heme-induced inflammation through its catabolic activity. Its byproduct CO reduces heme levels by complexing with Hb and avoiding heme release. These effects combine with its immunoregulatory and cytoprotective capacity to drive the protective effects in this phase of infection, increasing the disease tolerance. BV, biliverdin; Hb, hemoglobin; HO-1, heme oxygenase 1; iRBC, infected red blood cells; ROS, reactive oxygen species; TNF, tumor necrosis factor; TNFR, tumor necrosis factor receptor.
Fig 2.
(A) HO-1 promotes increased resistance in acute T. cruzi infection in mice. HO-1 expression reduces macrophage and heart parasitism and is associated with increased resistance to the infection during acute and chronic phases of the disease. (B) Up-regulation of HO-1 expression in macrophages reduces intracellular ROS and labile iron pool through FtH and ferroportin-1 expression. The net result is reduction of parasitism. FtH, ferritin H chain; HO-1, heme oxygenase 1; IFN, interferon; NRF2, nuclear factor erythroid 2-related factor 2; ROS, reactive oxygen species; Teff, T effector cells; TNF, tumor necrosis factor; Treg, regulatory T cell.
Fig 3.
HO-1 on Leishmania sp. Leishmania infection induces HO-1 on macrophages causing a reduction in intracellular levels of heme that affect gp91Phox activity and ROS generation.
NO and TNF production are also inhibited by HO-1. Thus, up-regulation of HO-1 expression increases parasitism and disease tolerance. gp91Phox, glycosylated 91-kDa phagocyte NADPH oxidase; HO-1, heme oxygenase 1; NO, nitric oxide; ROS, reactive oxygen species; TNF, tumor necrosis factor.
Fig 4.
In mice pretreated with chemical regulators of HO-1, induction of HO-1 expression decreases parasite burden on tissues and the morbidity of infected mice, while inhibition of HO-1 activity produced the opposite effect. This indicates that, in toxoplasmosis, HO-1 increases resistance and disease tolerance. HO-1, heme oxygenase 1.