Critical Role of Antimicrobial Peptide Cathelicidin for Controlling Helicobacter pylori Survival and Infection

Abstract

The antimicrobial peptide cathelicidin is critical for protection against different kinds of microbial infection. This study sought to elucidate the protective action of cathelicidin against Helicobacter pylori infection and its associated gastritis. Exogenous cathelicidin was found to inhibit H. pylori growth, destroy the bacteria biofilm, and induce morphological alterations in H. pylori membrane. Additionally, knockdown of endogenous cathelicidin in human gastric epithelial HFE-145 cells markedly increased the intracellular survival of H. pylori. Consistently, cathelicidin knockout mice exhibited stronger H. pylori colonization, higher expression of proinflammatory cytokines IL-6, IL-1β, and ICAM1, and lower expression of the anti-inflammatory cytokine IL-10 in the gastric mucosa upon H. pylori infection. In wild-type mice, H. pylori infection also stimulated gastric epithelium-derived cathelicidin production. Importantly, pretreatment with bioengineered Lactococcus lactis that actively secretes cathelicidin significantly increased mucosal cathelicidin levels and reduced H. pylori infection and the associated inflammation. Moreover, cathelicidin strengthened the barrier function of gastric mucosa by stimulating mucus synthesis. Collectively, these findings indicate that cathelicidin plays a significant role as a potential natural antibiotic for H. pylori clearance and a therapeutic agent for chronic gastritis.

Pathogenesis of Helicobacter pylori infection

“…The antimicrobial peptide cathelicidin has known activities against different microbial infections. Exogenous cathelicidin was recently found to inhibit H. pylori growth and disrupted bacterial biofilms . This study indicated that cathelicidin may function as natural antibiotic against H. pylori by reducing both the bacterial population and inflammation levels.…”

“…This study indicated that cathelicidin may function as natural antibiotic against H. pylori by reducing both the bacterial population and inflammation levels. Interestingly, cathelicidin also strengthened the barrier function of gastric mucosa by stimulating mucus synthesis . Another proposed way to treat H. pylori infection is utilizing fatty acids, because various studies have shown their antibacterial effects .…”

Host Defense Peptide Expression in Human Cervical Cells and Regulation by 1,25-Dihydroxyvitamin D3 in the Presence of Cytokines and Bacterial Endotoxin

“…It would be useful in future experiments to assess the functional impact of HVF and ECF with different concentrations of HDPs in terms of using bacterial killing assays. Moreover, there are published studies which demonstrate the antibacterial properties of both elafin and cathelicidn 42,43 .…”

“…More recently, cathelicidin has recently been shown inhibit H. pylori growth, destroy the bacteria biofilm, and induce morphological alterations in helicobacter pylori membrane 43 .…”

Helicobacter�pylori modulates cyclooxygenase‑2 and 15‑hydroxy prostaglandin dehydrogenase in gastric cancer

“…Multiple factors may be involved in the carcinogenesis of gastric cancer, including genetics and environmental factors. H. pylori is one of the most important environmental risk factors for gastric malignancies (13,14). Persistent inflammation in response to H. pylori infection is hypothesized to contribute to tumor cell proliferation and metastasis, and to affect survival (15,16).…”