TABLE 1.
Bacterial suppression of neutrophil respiratory burst
| Pathogen | Mechanism(s) |
|---|---|
| Anaplasma phagocytophilum | On internalization, the bacterium resides within a protective vacuole that excludes flavocytochromeb558103,104; down-regulates CYBB (gp91phox) gene expression.105 |
| Coxiella burnetii | Membrane translocation of p47phox and p67phox is inhibited, in part by the production of a diffusible acid phosphatase.106,107 |
| Francisella | Francisella tularensis (live vaccine strain) globally inhibits activation of respiratory burst by preventing flavocytochromeb558 as well as cytosolic p47phox and p67phox acquisition on phagosomes.108 Francisella novicida U112 produces an acid phosphatase that prevents phosphorylation and subsequent nuclear translocation of p47phox.109 |
| Helicobacter pylori | Although bacteria are internalized rapidly, O2− anions are produced extracellularly, but not inside phagosomes. p47phox, p67phox and gp91phox are excluded from the phagosome by unopsonized H. pylori strains.110 |
| Neisseria gonorrhoeae | Strains lacking Opacity (Opa)-Associated Protein on cell surface prevent the prevent p47phox recruitment to phagosomes.111 |
| Yersinia pestis | Produces YopE, a Type 3 secretion system (T3SS) effector protein that has GTPase like activity and inactivates Rac in neutrophils suppressing oxidative bust.112,113 |
| Pseudomonas aeruginosa | Produces T3SS effectors ExoS and ExoT that inhibit PI3K signaling essential for activation of NADPH oxidase.114 |
| Group A Streptococcus | Produces pore-forming toxin Streptolysin that inhibits NADPH oxidase activity via incompletely characterized mechanisms.115 |
| Bordetella pertussis | Produces adenylate cyclase toxin-hemolysin (CyaA) that breaks down ATP to cyclic-AMP to activate Src homology region 2 domain-containing phosphatase-1 (SHP-1). SHP-1 inactivates MAPKs (ERK and p38). This reduces p47phox phosphorylation and activation.116 |
| Bacillus anthracis | Produces lethal toxin (LTx) and edema toxin (EDx) that interfere with upstream MAPK signaling events preventing optimal activation of NADPH oxidase subunit and subsequent assembly of active enzyme complex. EDx can also upregulate conversion of ATP to cAMP and inhibit ROS via mechanism similar to CyaA.117 |