Abstract
The cellular formation of reactive oxygen species (ROS) represents an evolutionary ancient antimicrobial defense system against microorganisms. The NADPH oxidases (NOX), which are predominantly localized to endosomes, and the electron transport chain in mitochondria are the major sources of ROS. Like any powerful immunological process, ROS formation has costs, in particular collateral tissue damage of the host. Moreover, microorganisms have developed defense mechanisms against ROS, an example for an arms race between species. Thus, although NOX orthologs have been identified in organisms as diverse as plants, fruit flies, rodents, and humans, ROS functions have developed and diversified to affect a multitude of cellular properties, i.e., far beyond direct antimicrobial activity. Here, we focus on the development of NOX in phagocytic cells, where the so-called respiratory burst in phagolysosomes contributes to the elimination of ingested microorganisms. Yet, NOX participates in cellular signaling in a cell-intrinsic and -extrinsic manner, e.g., via the release of ROS into the extracellular space. Accordingly, in humans, the inherited deficiency of NOX components is characterized by infections with bacteria and fungi and a seemingly independently dysregulated inflammatory response. Since ROS have both antimicrobial and immunomodulatory properties, their tight regulation in space and time is required for an efficient and well-balanced immune response, which allows for the reestablishment of tissue homeostasis. In addition, distinct NOX homologs expressed by non-phagocytic cells and mitochondrial ROS are interlinked with phagocytic NOX functions and thus affect the overall redox state of the tissue and the cellular activity in a complex fashion. Overall, the systematic and comparative analysis of cellular ROS functions in organisms of lower complexity provides clues for understanding the contribution of ROS and ROS deficiency to human health and disease.
Highlights
The biological system involving the formation and scavenging of reactive oxygen species (ROS) emerged more than 3 billion years ago, together with the appearance of photosynthetic organisms (Inupakutika et al, 2016)
We focus on the role of NADPH oxidases (NOX) and ROS signaling in professional phagocytes, where ROS have mainly been studied for their role in pathogen elimination
Stimulation of other receptors, including Fc and integrin receptors, and the G-protein-coupled receptors (GPCRs) recognizing N-Formylmethionineleucyl-phenylalanine result in direct activation of NOX2 (Nguyen et al, 2017). Their interaction with enzymes such as phospholipase C leads to the activation of protein kinase C (PKC) family members, which phosphorylate the cytosolic subunits of NOX2
Summary
The biological system involving the formation and scavenging of reactive oxygen species (ROS) emerged more than 3 billion years ago, together with the appearance of photosynthetic organisms (Inupakutika et al, 2016). ROS in Phagocytes function and integral to cellular signaling in most organisms. NADPH oxidases (NOX), as major sources of ROS, play an important role in this context. Within this group, the phagocyte NADPH oxidase (NOX2) is the best-studied member. The phagocyte NADPH oxidase (NOX2) is the best-studied member It generates large amounts of ROS in phagosomes, which function to kill ingested microbes in a direct or indirect fashion. Mitochondria contribute substantial amounts of ROS during oxidative phosphorylation (Hamanaka and Chandel, 2010) These pathways require tight regulation, as excessive ROS produced by phagocytes may cause oxidative stress and damage in the tissues and contribute to e.g., neurodegeneration (Wu et al, 2006). We will compare ROS formation and function in phagocytes of different species and discuss the impact of phagocyte-derived ROS on cellular and tissular signaling
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
