Reactive species and pathogen antioxidant networks during phagocytosis

Abstract

The generation of phagosomal cytotoxic reactive species (i.e., free radicals and oxidants) by activated macrophages and neutrophils is a crucial process for the control of intracellular pathogens. The chemical nature of these species, the reactions they are involved in, and the subsequent effects are multifaceted and depend on several host- and pathogen-derived factors that influence their production rates and catabolism inside the phagosome. Pathogens rely on an intricate and synergistic antioxidant armamentarium that ensures their own survival by detoxifying reactive species. In this review, we discuss the generation, kinetics, and toxicity of reactive species generated in phagocytes, with a focus on the response of macrophages to internalized pathogens and concentrating on Mycobacterium tuberculosis and Trypanosoma cruzi as examples of bacterial and parasitic infection, respectively. The ability of pathogens to deal with host-derived reactive species largely depends on the competence of their antioxidant networks at the onset of invasion, which in turn can tilt the balance toward pathogen survival, proliferation, and virulence over redox-dependent control of infection.

Glycolytic reprograming in Salmonella counters NOX2-mediated dissipation of ΔpH

“…Despite its paramount role in host defense, our understanding of the molecular mechanisms by which NOX2 exerts its powerful antimicrobial activity remains a subject of contention [2][3][4][5] . It is widely accepted that reactive oxygen species generated in the respiratory burst damage DNA via Fenton-mediated chemistry and oxidize protein cysteine residues and metal cofactors in regulatory and metabolic proteins [6][7][8] . However, others have argued that phagocytic superoxide primarily damages extracytoplasmic targets 9 .…”

“…However, others have argued that phagocytic superoxide primarily damages extracytoplasmic targets 9 . How the bacterium mitigates this attack is also only partly understood 4,6,7,9 .…”

Flying by the seat of our pants: is low dose radiation therapy for COVID-19 an option?

“…Such redox shifts are tightly integrated with metabolic pathway alterations and generate oxidant-anti-oxidant signaling loops that continuously monitor the redox state and feed back to restore homeostasis (Forrester et al 2018). The importance of ROS in defense against pathogens is most dramatically seen during the respiratory/oxidative burst by macrophages and neutrophils (Baldridge and Gerard 1932;Piacenza et al 2019). It is linked to activation of the pentose phosphate pathway that, amongst other functions, enables anti-oxidant signaling, provides reducing equivalents (i.e., NADPH) for the cell, and plays an important role in antimicrobial host defense and inflammation by fueling NADPH oxidase.…”

SHIP-1 Regulates Phagocytosis and M2 Polarization Through the PI3K/Akt–STAT5–Trib1 Circuit in Pseudomonas aeruginosa Infection

“…Furthermore, WT mice and SHIP-1 −/− mice were anesthetized using 45 mg/kg of ketamine and instilled intranasally with 2 × 10 7 CFUs of PAO1 for 12 h; the lipid peroxidation was measured in the lung (Figure 2B), liver (Figure S2A), and spleen (Figure S2B). The oxidation state of the tissue and increased recruitment of PMNs and MPO activity are well-recognized for indicating the endpoints of acute lung injury (38,39). To further assess the damage of lung tissue in SHIP-1 −/− mice, the amount of reactive oxygen species (ROS) released and cellular superoxide was measured by using NBT (Figure 2C) and H 2 DCF assay (Figure 2D).…”