Phagocytosis is a crucial host defense mechanism. Mutations or treatments resulting in reduced phagocytic function predispose the host to bacterial infections, especially infections caused by certain organisms (Table 1):
(1) Children with genetic defects in phagocytosis have an increased number and severity of infections. Two examples of these defects are chronic granulomatous disease, where the phagocyte cannot kill the ingested bacteria due to a defect in NADPH oxidase, which results in a failure to generate H2O2; Chédiak–Higashi syndrome, involving abnormal lysosomal granules that don’t fuse with the phagosome, and are subsequently unable to kill bacteria.
(2) Frequent infections occur in neutropenic patients, especially when the PMN count drops below 500/μL as a result of immunosuppressive drugs or irradiation. These infections are frequently caused by opportunistic organisms (i.e., organisms that rarely cause disease in people with normal immune systems). (3) Splenectomy removes an important source of both phagocytes and immunoglobulins, and predisposes to sepsis caused by three encapsulated bacteria: Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Streptococcus pneumoniae causes approximately 50% of episodes of sepsis in splenectomized patients. Patients with sickle cell anemia and other hereditary anemias can autoinfarct their spleen, resulting in a loss of splenic function and a predisposition to sepsis caused by these bacteria.
(4) People who have diabetes mellitus, especially those who have poor glucose control or episodes of ketoacidosis, have an increased number of, and more severe, infections compared with people who do not have diabetes. The main host defense defect in these patients is reduced neutrophil function, especially when hyperglycemia and acidosis occur.
Table1. Reduced Phagocytosis Predisposes to Infection Caused by Certain Bacteria
Two specific diseases highly associated with diabetes are malignant otitis externa caused by P. aeruginosa and mucor mycosis caused by molds belonging to the genera Mucor and Rhizopus. In addition, there is an increased incidence and severity of community-acquired pneumonia caused by bacteria such as S. pneumoniae and S. aureus, urinary tract infections caused by organisms such as E. coli and C. albicans, and Candidal vulvovaginitis. Diabetic patients also have many foot infections because atherosclerosis compromises the blood supply and necrosis of tissue occurs. Skin infections, such as ulcers and cellulitis, and soft tissue infections, such as necrotizing fasciitis, are common and can extend to the underlying bone, causing osteo myelitis. Staphylococcus aureus and mixed facultative anaerobic bacteria are the most common causes.
