Host heme oxygenase‐1: Friend or foe in tackling pathogens?

Abstract

Infectious diseases are a major challenge in management of human health worldwide. Recent literature suggests that host immune system could be modulated to ameliorate the pathogenesis of infectious disease. Heme oxygenase (HMOX1) is a key regulator of cellular signaling and it could be modulated using pharmacological reagents. HMOX1 is a cytoprotective enzyme that degrades heme to generate carbon monoxide (CO), biliverdin, and molecular iron. CO and biliverdin (or bilirubin derived from it) can restrict the growth of a few pathogens. Both of these also induce antioxidant pathways and anti-inflammatory pathways. On the other hand, molecular iron can induce proinflammatory pathway besides making the cellular environment oxidative in nature. Since microbial infections often induce oxidative stress in host cells/tissues, role of HMOX1 has been analyzed in the pathogenesis of number of infections. In this review, we have described the role of HMOX1 in pathogenesis of bacterial infections caused by Mycobacterium species, Salmonella and in microbial sepsis. We have also provided a succinct overview of the role of HMOX1 in parasitic infections such as malaria and leishmaniasis. In the end, we have also elaborated the role of HMOX1 in viral infections such as AIDS, hepatitis, dengue, and influenza. © 2018 IUBMB Life, 70(9):869-880, 2018.

Modulation of Iron Metabolism in Response to Infection: Twists for All Tastes

“…This leads to increased levels of free hemoglobin and heme in the plasma, which in turn increases the production and release of hemopexin and haptoglobin, and also increases the expression of HO-1 in several tissues. Whether HO-1 activation is protective and/or detrimental for the host is a matter of discussion (reviewed in [ 79 ]). HO-1 expression in macrophages is induced upon an infection by mycobacteria and salmonella, both in vitro and in vivo.…”

Heme oxygenase-1 in protozoan infections: A tale of resistance and disease tolerance

“…Given its critical role in homeostasis [7][8][9][10], it is not surprising that HO-1 profoundly affects the host response to infection in multiple ways [4,[11][12][13]. There are 2 main ways that a host deals with infection; one is through resistance, the ability to restrict or eliminate the infectious agent, a function primarily performed by the immune system.…”

Heme Oxygenase-1 Induction by Blood-Feeding Arthropods Controls Skin Inflammation and Promotes Disease Tolerance

“…Under inflammatory conditions, oxidative stress promotes release of free heme from oxidized hemoproteins, such as hemoglobin (Hb), eliciting the production of free radicals (Gozzelino et al, 2010). Heme oxygenase (HO)-1 is a stress-responsive enzyme that catabolizes the rate-limiting reaction of heme degradation, generating equimolar amounts of Fe, carbon monoxide (CO), and biliverdin (Gozzelino et al, 2010;Singh et al, 2018). Its enzymatic activity has broad cytoprotective and immunoregulatory effects targeting a plethora of genes involved in stress responses (Otterbein et al, 2003).…”