The role of the neutrophil and phagocytosis in infection caused by Helicobacter pylori Lee-Ann H. Allen Recent advances in our understanding of Helicobacter pylori– phagocyte interactions indicate that these organisms actively modulate phagocyte function in order to retard phagocytosis, while simultaneously inducing a strong respiratory burst. The central players in this dynamic include H. pylori neutrophil activating protein and factors that are associated with the cag pathogenicity island type IV secretion apparatus. Additionally, catalase, alkyl hydroperoxide reductase, and factors that are unique to type I strains allow bacteria to resist phagocytic killing. Curr Opin Infect Dis 14:273–277. # 2001 Lippincott Williams & Wilkins. Department of Medicine, Division of Infectious Diseases, and the Inflammation Program, University of Iowa and the Veterans Affairs Medical Center, Iowa City, Iowa, USA Correspondence to Dr Lee-Ann Allen, Department of Medicine, University of Iowa, 200 Hawkins Drive, SW34-GH, Iowa City, IA 52242, USA Tel: +1 319 356 8287; fax: +1 319 356 4600; e-mail: lee-ann-allen@uiowa.edu Current Opinion in Infectious Diseases 2001, 14:273–277 Abbreviations AhpC alkyl hydroperoxide reductase HP-NAP Helicobacter pylori neutrophil activating protein NAC nonopsonic neutrophil-activating component NADPH nicotinamide adenine dinucleotide phosphate, reduced form PAI pathogenicity island PMN polymorphonuclear neutrophil # 2001 Lippincott Williams & Wilkins 0951-7375 Introduction Helicobacter pylori is a highly successful human pathogen that has spread throughout the world. These organisms establish a chronic infection in the gastric mucosa that results in gastritis, peptic ulceration, or more rarely gastric cancer [1,2 . ]. In most cases, infection occurs in childhood and persists for life in the absence of antibiotic treatment. One hallmark of H. pylori infection is chronic inflammation, and phagocytes, particularly neutrophils [polymorphonuclear neutrophils (PMNs)], populate the gastric mucosa [1,2 . ]. Many virulence factors contribute to H. pylori pathogenesis [1,3 . ]. Urease and flagella are found in all H. pylori strains, and are required for colonization. Other factors such as VacA vary in sequence and bioactivity, and still other virulence factors are found in only a fraction of H. pylori isolates. Most prominently, a subset of H. pylori strains contain the cag pathogenicity island (PAI), which encodes a type IV secretion apparatus. Strains containing the cag PAI are more prevalent in persons with ulcer disease, and induce more inflammation and tissue damage than do less virulent, cag-negative isolates [1,3 . ]. It is well established that phagocyte density correlates with the ability of H. pylori to induce tissue damage [1,2 . ,3 . ], and it is believed that host and bacterial factors collaborate in this endeavor. However, one issue that remains unresolved is how H. pylori survives in a phagocyte-rich environment. The focus of this brief review is limited to discoveries published in the past year. During this short time significant advances have been made both in our understanding of the molecular mechanisms that govern neutrophil migration and activation during H. pylori infection, and in the identification of virulence factors that confer resistance to phagocytic killing. Neutrophil recruitment to the gastric mucosa In response to gradients of chemotactic factors, leuko- cytes upregulate adhesion receptors and migrate out of the bloodstream to sites of infection. H. pylori induces a state of ‘chronic acute inflammation’, in which neutro- phils outnumber macrophages in the infected gastric mucosa [2 . ,3 . ]. In addition, it is well documented that individual strains of H. pylori differ in their ability to promote phagocyte recruitment, and type I organisms that contain the cag PAI promote more inflammation than do less virulent, type II strains [1,2 . ,3 . ]. Signifi- cantly, at least four H. pylori virulence factors have now been identified that directly or indirectly modulate 273