Neutrophils and mononuclear cells from patients with chronic granulomatous disease release nitric oxide.

Carbohydrate Oxidation Acidifies Endosomes, Regulating Antigen Processing and TLR9 Signaling

“…In agreement with our findings, the NADPH oxidase complex that produces superoxide is effective only at near-neutral pH, because a more neutral environment has been found to be more conducive to oxidation-mediated killing of pathogens (36). Interestingly, phagocytes isolated from chronic granulomatous disease (CGD) model mice, a primary immunodeficiency in which a genetic defect in the NADPH oxidase results in diminished reactive oxygen species production, have been shown to contain more acidic phagosomes than seen in normal WT cells and are thus unable to kill ingested pathogens (37–39) despite the presence of normal to high concentrations of NO (40, 41). Given our findings, it is not surprising that patients with CGD are particularly susceptible to infection by heavily encapsulated microbes (42, 43), including Staphylococcus aureus that carry T cell activating GlyAgs in their capsule (44) and Aspergillus species.…”

Increased production of nitric oxide by neutrophils from patients with chronic granulomatous disease on interferon-gamma treatment

“…Since this reaction is not occurred in CGD, NO by itself may be of a relatively larger importance [15]. Moreover, it has been shown that PMNs from CGD patients produce NO in vitro [18]. We speculated that the effect of IFN-γ on NO production would be one of the probable underlying mechanisms explaining the therapeutic effect of IFN-γ in patients with CGD.…”

Perspectives series: host/pathogen interactions. Mechanisms of nitric oxide-related antimicrobial activity.

“…Elevations in NOS2 protein expression by circulating mononuclear cells have been correlated with increased systemic NO production in Tanzanian children with malaria (3). Similarly, striking increases in NOS2 protein have been found in macrophages from patients with active pulmonary tuberculosis (7), acute respiratory distress syndrome, glomerulonephritis, and rheumatoid arthritis (19), and other evidence of macrophage-derived NO has been obtained from patients with alcoholic hepatitis or chronic granulomatous disease (20). One report even suggests that NO production by macrophages obtained from patients with active tuberculosis may approach levels of production by murine cells (21), although this observation awaits confirmation.…”