Journal of Hepatology and Gastrointestinal disorders
Open Access

Host Immune Response Mechanisms and Therapies of Helicobacter pylori

Dan Turell^{* *}Correspondence: Dan Turell, Department of Microbiology, Copenhagen University, Copenhagen, Denmark, Email:

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About the Study

A gram-negative bacterium called Helicobacter pylori has evolved specifically to thrive in the stomach acid of humans. It colonizes the gastric mucosa and is implicated in the pathogenesis of various gastrointestinal disorders, notably chronic gastritis, peptic ulcers, and even gastric cancer. H. pylori infection is prevalent worldwide, affecting approximately half of the global population. Its ability to persist in the stomach is attributed to several virulence factors, including urease production, which neutralizes stomach acid, and flagella for motility. The bacterium interacts with host immune responses, leading to chronic inflammation and tissue damage over time. While eradication therapy involving antibiotics and proton pump inhibitors is effective, rising antimicrobial resistance poses challenges. Research also suggests potential links between H. pylori infection and extra-gastric conditions like cardiovascular diseases and neurodegenerative disorders, highlighting the bacterium's broader impact on human health beyond the digestive system.

Host immune response

Helicobacter pylori elicits a complex host immune response upon colonization of the gastric mucosa. Initially, the bacterium's presence triggers innate immune mechanisms, such as the activation of macrophages and neutrophils, which release cytokines and chemokines to recruit more immune cells to the site of infection. Adaptive immune responses play a vital role in controlling H. pylori, with T cells, particularly CD⁴⁺ T cells, and B cells producing specific antibodies against bacterial antigens. However, H. pylori has evolved mechanisms to evade immune surveillance, including antigenic variation and modulation of host immune signaling pathways. Chronic infection often results in persistent inflammation characterized by the infiltration of lymphocytes and plasma cells into the gastric mucosa. Understanding the dynamics of host immune responses to H. pylori is necessary for developing targeted therapeutic strategies and vaccines aimed at enhancing protective immunity against this persistent pathogen.

Role in gastric cancer development

Helicobacter pylori plays a significant role in the development of gastric cancer, particularly intestinal-type adenocarcinoma. Chronic infection with H. pylori leads to sustained inflammation and damage to the gastric epithelium, which can progress through stages of chronic gastritis, gastric atrophy, intestinal metaplasia, and dysplasia, ultimately culminating in cancerous transformation. The bacterium's virulence factors, such as Cytotoxin-Associated Gene A (CagA) and Vacuolating cytotoxin A (VacA), contribute to cellular alterations and genomic instability within gastric cells, promoting oncogenic pathways. Additionally, H. pylori-induced chronic inflammation stimulates the production of reactive oxygen and nitrogen species, further enhancing mutagenesis and tumor progression. Efforts to reduce gastric cancer incidence include H. pylori eradication strategies in high-risk populations and recent research into preventive vaccines targeting key bacterial antigens. Understanding these mechanisms is important for developing effective interventions to mitigate the oncogenic potential of H. pylori infection.

Evasion mechanisms

Helicobacter pylori employs sophisticated evasion mechanisms to persistently colonize the hostile environment of the human stomach. One key strategy involves antigenic variation, where H. pylori modifies surface proteins to evade recognition by the host immune system, thus avoiding immune clearance. The bacterium also manipulates host immune responses by secreting virulence factors like CagA and VacA, which disrupt signaling pathways within host cells, impairing immune cell function and promoting bacterial survival. Additionally, H. pylori can modulate the gastric microenvironment by inducing regulatory T cells and suppressing pro-inflammatory responses, creating a tolerogenic niche favourable for its persistence. Furthermore, the bacterium can form biofilms and adhere tightly to gastric epithelial cells, shielding itself from antibiotics and immune attacks.

Alternative Therapeutic Approaches

These are emerging due to increasing antibiotic resistance and treatment failures. One approach involves probiotics, such as Lactobacillus and Bifidobacterium species, which aim to restore gastric microbial balance and compete with H. pylori for colonization sites. Another potential strategy is immunotherapy, using vaccines that target specific H. pylori antigens to stimulate protective immune responses. These vaccines aim to prevent initial colonization or reduce bacterial load in infected individuals, potentially improving treatment outcomes and reducing recurrence rates. Furthermore, natural products like cranberry extracts and green tea polyphenols show antimicrobial activity against H. pylori and may complement standard antibiotic therapies. Combination therapies, integrating multiple approaches like probiotics with traditional antibiotics, are also being investigated to improve treatment efficacy and overcome resistance.