Differential inflammatory response to Helicobacter pylori infection: etiology and clinical outcomes

Jonathan Richard White,1 Jody Anne Winter,2 Karen Robinson1 1NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust and The University of Nottingham, Nottingham, 2Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK Abstract: The bacterial pathogen Helicobacter pylori commonly colonizes the human gastric mucosa during early childhood and persists throughout life. The organism has evolved multiple mechanisms for evading clearance by the immune system and, despite inducing inflammation in the stomach, the majority of infections are asymptomatic. H. pylori is the leading cause of peptic ulcer disease and gastric cancer. However, disease outcomes are related to the pattern and severity of chronic inflammation in the gastric mucosa, which in turn is influenced by both bacterial and host factors. Despite over 2 decades of intensive research, there remains an incomplete understanding of the circumstances leading to disease development, due to the fascinating complexity of the host–pathogen interactions. There is accumulating data concerning the virulence factors associated with increased risk of disease, and the majority of these have pro-inflammatory activities. Despite this, only a small proportion of those infected with virulent strains develop disease. Several H. pylori virulence factors have multiple effects on different cell types, including the induction of pro- and anti-inflammatory, immune stimulatory, and immune modulatory responses. The expression of multiple virulence factors is also often linked, making it difficult to assess the meaning of their effects in isolation. Overall, H. pylori is thought to usually modulate inflammation and limit acute damage to the mucosa, enabling the bacteria to persist. If this delicate balance is disturbed, disease may then develop. Keywords: Helicobacter pylori, inflammation, mucosal immunity, peptic ulcer disease, gastric cance