Defective priming of the phagocyte oxidative burst in a child with recurrent intracellular infections

Human phagocytes (polymorphonuclear neutrophils and monocytes) play a criti cal role in host defense against invading microorganisms. Recent studies re ported that circulating phagocytes undergo a final maturation process, in p articular in terms of oxidative burst, during extravasation and migration t o local sites of inflammation. This process is known as priming. We report here on a nine-year-old boy with successive disseminated infections due to intracellular microorganisms (Mycobacterium bovis, BCG, and Salmonella typh imurium). No T- or B-cell quantitative or qualitative defects were found. P olymorphonuclear neutrophil (PMN migration and NADPH oxidase in PMNs and mo nocytes stimulated with various agents at optimal concentrations were norma l, ruling out a leukocyte adhesion deficiency syndrome, a Chediak Higashi s yndrome, and a chronic granulomatous disease. Nevertheless, the patient's P MNs and monocytes showed defective priming capacity, as measured by H2O2 pr oduction after pretreatment with LPS (5 mu g/mL for 30 min), TNF alpha (100 units/mL for 30 min), or IL-8 (50 ng/mL for 30 min) in response to bacteri al N-formyl peptides (fMLP 10(-6) M for 5 min). In these conditions, H2O2 p roduction of PMNs and monocytes from the patient did not exceed that of the samples treated with fMLP or LPS alone, while the controls strongly produc ed H2O2. Moreover, monocytes from the patient showed an impaired capacity t o kill S. typhimurium in vitro. Such an impairment could be related at leas t in part to the priming deficiency of phagocyte oxidative burst. This case suggests, for the first time, that in vivo priming processes are critical in host defence against intracellular pathogens. (C) Elsevier, Paris.