Oxidative killing of microbes by phagocytes represents a leading edge of the innate immune response. AZD5363 nmr The released microbial contents following

killing also serve as a pool of potential antigens for the adaptive immune response within the endosomal class II major histocompatibility complex (MHCII) pathway. Oxidation is achieved through the production of both reactive oxygen species ROS and reactive nitrogen species (RNS) that attack surface molecules and lyse pathogens. The primary source of reactive nitrogen species is NO synthesized by the inducible nitric oxide synthase (iNOS) enzyme 1, which is transcriptionally activated via the NF-κB signaling cascade upon recognition of microbial “molecular patterns” at the cell surface 2. The NADPH oxidase complex is responsible for the production of superoxide, which fuels the synthesis of hydrogen peroxide and hypochlorous acid through the serial enzymatic

actions of superoxide dismutase and myeloperoxidase respectively 3, 4. Chronic granulomatous disease (CGD) is characterized by any of a number of deleterious mutations within the NADPH oxidase complex 5–7. While the reduction Selleck Talazoparib of superoxide production varies in severity depending on the mutation, patients with CGD show heightened susceptibility to bacterial and fungal infections, have increased incidence of abscess and granuloma formation, and suffer from chronic inflammation 7–9, all of which highlight the central role for oxidation in controlling infectious disease. Although CGD is classified as a primary immunodeficiency, the increases Sitaxentan in abscess and granuloma formation

as well as the chronic unresolved inflammation represent hyperresponsiveness to infection and microbial products 8–10. The granulomas are often sterile and form in response to unregulated and widespread inflammation 7–11. In contrast, abscess formation is a T-cell-dependent adaptive pathway 12 that normally serves to quarantine the offending pathogen. Despite the role in reducing dissemination of the pathogen throughout the body, abscesses reduce the efficacy of antibiotics due to isolation of the bacteria from the blood stream and they require surgical drainage, collectively increasing risk of secondary infections 8. CGD patients are susceptible to abscess formation induced by microbes carrying antigenic capsular carbohydrates, including the fungus Aspergillus sp., the Gram-positive Staphylococcus aureus, and other catalase-positive organisms 7, 13. Bacteroides fragilis, also catalase-positive, is the most common anaerobic bacteria isolate from clinical abscess samples 14, and both S. aureus and B.