Cathelicidin encoded Lactococcus lactis protects against Helicobacter pylori infection and inflammation in mice

Abstract

Cathelicidin has been shown to modulate microbial growth, wound healing, and cancer development. However, its role in Helicobacter pylori (H. pylori) infection and inflammation in stomachs remains unexplored. This study sought to elucidate the actions of mouse cathelicidin (mCRAMP) in protection against H. pylori infection and inflammation in mice. Cathelicidin wild‐type (Cnlp+/+) and knockout (Cnlp−/−) mice were given orally once every two days with mCRAMP‐encoded Lactococcu lactis (L. lactis) for two weeks before H. pylori challenge in stomachs. This treatment continued for a further two months. Stomachs were then excised for assessment of H. pylori infection and inflammation. Results showed that L. lactis could harbor and secrete mCRAMP in the gastric mucosa. In the absence of cathelicidin, Cnlp−/− mice exhibited stronger H. pylori colonization together with higher inflammation score and marked tumor necrosis factor (TNF‐α) and interleukin‐6 (IL‐6) expressions in the gastric mucosa. H. pylori infection however by itself stimulated gastric epithelium‐ and neutrophil‐derived mCRAMP production in Cnlp+/+ mice. To further confirm the importance of cathelicidin on these pathological conditions, pre‐treatment with mCRAMP‐encoded L. lactis significantly increased mucosal mCRAMP level in both types of animals and reduced H. pylori infection and also TNF‐α and IL‐6 mRNA expressions. These findings indicate that the food‐grade probiotic encoded with cathelicidin protects against H. pylori infection and gastritis in vivo. (Grant support: Research Fund for Control of Infectious Diseases, Food and Health Bureau, Hong Kong)