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

Abstract

Human phagocytes (polymorphonuclear neutrophils and monocytes) play a critical role in host defense against invading microorganisms. Recent studies reported that circulating phagocytes undergo a final maturation process, in particular in terms of oxidative burst, during extravasation and migration to 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 typhimurium). No T- or B-cell quantitative or qualitative defects were found. Polymorphonuclear neutrophil (PMN) migration and NADPH oxidase in PMNs and monocytes stimulated with various agents at optimal concentrations were normal, ruling out a leukocyte adhesion deficiency syndrome, a Chediak Higashi syndrome, and a chronic granulomatous disease. Nevertheless, the patient's PMNs and monocytes showed defective priming capacity, as measured by H(2)O(2) production after pretreatment with LPS (5 microg/mL for 30 min), TNFalpha (100 units/mL for 30 min), or IL-8 (50 ng/mL for 30 min) in response to bacterial N-formyl peptides (fMLP 10(-6) M for 5 min). In these conditions, H(2)O(2) production of PMNs and monocytes from the patient did not exceed that of the samples treated with fMLP or LPS alone, while the controls strongly produced H(2)O(2). Moreover, monocytes from the patient showed an impaired capacity to kill S. typhimurium in vitro. Such an impairment could be related at least 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.

• Authors: C Elbim, P Rajagopalan-Levasseur, S Chollet-Martin, J L Gaillard, M Fay, J Hakim, A Fischer, J L Casanova, M A Gougerot-Pocidalo
• Journal: Microbes and infection (Microbes Infect) Vol. 1 Issue 8 Pg. 581-7 (Jul 1999) ISSN: 1286-4579 [Print] France
• PMID: 10611734 (Publication Type: Journal Article)

Chemical References

• Cytochrome c Group
• Cytokines
• Lipopolysaccharides
• N-Formylmethionine Leucyl-Phenylalanine
• Hydrogen Peroxide
• NADPH Oxidases

Topics

• Adult
• Cells, Cultured
• Chemotaxis, Leukocyte (drug effects)
• Child
• Consanguinity
• Cytochrome c Group (metabolism)
• Cytokines (pharmacology)
• Female
• Genes, Recessive
• Humans
• Hydrogen Peroxide (blood, metabolism)
• Lipopolysaccharides (pharmacology)
• Male
• Monocytes (drug effects, metabolism, microbiology, pathology)
• Mycobacterium bovis (immunology, physiology)
• N-Formylmethionine Leucyl-Phenylalanine (pharmacology)
• NADPH Oxidases (metabolism)
• Neutrophils (drug effects, metabolism, microbiology, pathology)
• Phagocyte Bactericidal Dysfunction (enzymology, immunology, metabolism, pathology)
• Recurrence
• Respiratory Burst (drug effects)
• Salmonella Infections (enzymology, immunology, metabolism, pathology)
• Salmonella typhimurium (immunology, physiology)