Fungal Phagocytosis in the Absence of Oxidative Stress Response Proteins

Reactive oxygen species (ROS) are crucial in cell metabolism and homeostasis. ROS can damage biomolecules and organelles. To date, the paradigm is that ROS are integral components of cellular signaling and various cellular functions. The widely used concept of “oxidative stress” has been refined into “oxidative distress,” wherein ROS reach damaging levels, and “oxidative eustress,” wherein ROS do not cause damage and contribute to homeostasis. However, it is essential to maintain a prooxidant/antioxidant balance. ROS play a significant role in medically relevant fungi and human health, including inflammation, cancer, metabolic diseases, and aging. The innate immune system is critical in defending against pathogenic fungi. Macrophages and other phagocytic immune cells, which are derived from monocyte differentiation, are involved in the first line of defense during microbial invasion. Several pathogenic fungi have developed mechanisms to evade phagocytosis. Antioxidant enzymes are vital in this context. For example, an opportunistic human fungal pathogen, relies on its ability to escape destruction by phagocytosis and the immune system. Its antioxidant defenses include the thioredoxin system (TrxR), peroxiredoxin (Prx), superoxide dismutases (SODs), catalases (CATs), and the glutathione system, which consists of glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), and glutaredoxin (Grx). In this chapter, we address the consequences of deleting or removing important genes involved in antioxidant defenses to observe the response to ROS.