Role of haem oxygenase-1 in microbial host defence

Abstract

Haem oxygenase (HO)-1 is a cytoprotective enzyme that plays a critical role in defending the body against oxidant-induced injury during inflammatory processes. HO catalydes the degradation of haem to carbon monoxide (CO), biliverdin and ferrous iron. Biliverdin is converted to bilirubin, a potent endogenous antioxidant. CO has a number of biological functions, including anti-inflammatory properties. In various models of disease, HO-1 is known to play a critical role by ameliorating the pathological consequences of injury. In many of these models, the beneficial effects of HO-1 and its products of haem catabolism are by suppressing an inflammatory response. However, when investigating diseases due to microbial infections, inhibition of the inflammatory response could disrupt the ability of the immune system to eradicate an invading pathogen. Thus, questions remain regarding the role of HO-1 in microbial host defence. This microreview will address our present understanding of HO-1 and its functional significance in a variety of microbial infections.

Fig. 1. The HO-1 pathway and its effect on microbial infections

Microbial infections that may involve the HO-1 pathway include those due to bacteria (polymicrobial, gram-positive, and gram negative); mycobacteria; fungi; viruses including hepatitis B virus (HBV), hepatitis C virus (HCV), HIV (and its complication Kaposi’s sarcoma – KS), and influenza; and the parasitic species leading to malaria (both the exoerythrocytic liver stage and the erythrocytic blood stage). These microbes may lead to either disseminated disease (which may result in sepsis) or organ specific infections. Microbial infections typically lead to an induction of HO-1, which degrades heme generating carbon monoxide (CO), biliverdin-IXα (subsequently reduced to biliverdin-IXα, and iron. These metabolites have a number of properties including the anti-inflammatory and pro-phagocytic effects of CO, and the anti-oxidant and anti-inflammatory properties of biliverdin/bilirubin. The properties of HO-1, and the products of heme catabolism, then have an ability to suppress (−) the microbial response or promoter (+) microbial survival.