Redox regulation of immunity and the role of small molecular weight thiols

Abstract

It is thought that excessive production of reactive oxygen species (ROS) can be a causal component in many diseases, some of which have an inflammatory component. This led to an oversimplification whereby ROS are seen as inflammatory and antioxidants anti-inflammatory. This paper aims at reviewing some of the literature on thiols in host defense. The review will first summarize the mechanisms by which we survive infections by pathogens. Then we will consider how the redox field evolved from the concept of oxidative stress to that of redox regulation and how it intersects the field of innate immunity. A third section will analyze how an oversimplified oxidative stress theory of disease led to a hypothesis on the role of ROS and glutathione (GSH) in immunity, respectively as pro- and anti-inflammatory mediators. Finally, we will discuss some recent research and how to think out of the box of that oversimplification and link the role of thiols in redox regulation to the mechanisms by which we survive an infection outlined in the first section.

Keywords: Glutathione; HIF-1α; Inflammation; Innate immunity; NF-kB; Nrf2.

Graphical abstract

Fig. 1

Resistance and tolerance as the two mechanisms to survive infections.

Fig. 2

Regulators (yellow) and effectors (red) of resistance and tolerance. Left: innate immunity controls pathogens by ROS production by phagocytes (mainly antibacterial) and upregulation of the IFN pathway (mainly antiviral) as well as activation of the inflammatory response through activation of NFkB. Right: tolerance includes tissue protection by Nrf2-mediated upregulation of antioxidant systems and HIF-1-mediated induction of tissue-protective cytokines (e.g. EPO) as well as promotion of tissue repair through induction of growth factors (e.g. VEGF). Please note the dual role of ROS and GSH both as effectors and regulators. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)