Host defense mechanisms against intracellular bacterial pathogens. (A) Host-derived antimicrobial ROS and RNS (highlighted in yellow). Host proteins are in blue boxes, and bacterial detoxification enzymes are in red boxes. NADPH oxidase (NOX) and inducible nitric oxide synthase (iNOS) are recruited to the phagosome in the respiratory burst. Myeloperoxide (MPO) is a significant component of neutrophil granules but is also found in phagolysosomes (97). Superoxide dismutase (SOD), catalase (Kat), and peroxiredoxins (Prx) detoxify ROS, while flavohemoglobin (Hmp) and flavorubredoxin (NorV) detoxify RNS. At low pH, peroxynitrite will be protonated (ONOOH [24]). Similarly, superoxide is protonated in the phagolysosome to form the reactive HO2˙ species (13). (B) Simplified schematic depicting macrophage phagosomal maturation (97). The pH of the phagosome steadily decreases, according to the pH scale shown, via recruitment of the vacuolar ATPase (vATPase). The bacterium is in gray. Not drawn to scale.