TFF1 Induces Aggregation and Reduces Motility of Helicobacter pylori

Abstract

Gastric cancer is considered one of the most common malignancies in humans and Helicobacter pylori infection is the major environmental risk factor of gastric cancer development. Given the high spread of this bacterium whose infection is mostly asymptomatic, H. pylori colonization persists for a long time, becoming chronic and predisposing to malignant transformation. The first defensive barrier from bacterial infection is constituted by the gastric mucosa that secretes several protective factors, among which is the trefoil factor 1 (TFF1), that, as mucin 5AC, binds the bacterium. Even if the protective role of TFF1 is well-documented, the molecular mechanisms that confer a beneficial function to the interaction among TFF1 and H. pylori remain still unclear. Here we analyze the effects of this interaction on H. pylori at morphological and molecular levels by means of microscopic observation, chemiotaxis and motility assays and real-time PCR analysis. Our results show that TFF1 favors aggregation of H. pylori and significantly slows down the motility of the bacterium across the mucus. Such aggregates significantly reduce both flgE and flaB gene transcription compared with bacteria not incubated with TFF1. Finally, our results suggest that the interaction between TFF1 and the bacterium may explain the frequent persistence of H. pylori in the human host without inducing disease.

Differential Transcriptomic Profiles Following Stimulation with Lipopolysaccharide in Intestinal Organoids from Dogs with Inflammatory Bowel Disease and Intestinal Mast Cell Tumor

“…LPS has also been shown to induce OAS in marine sponges [ 55 ]. TAP2 and trefoil factor 1 (TFF1) upregulation in IBD enteroids and colonoids following LPS treatment could result from their ability to modulate TLR4 signaling or their anti-inflammatory properties [ 97 , 98 , 99 ]. TAP2 has been shown to inhibit TLR4 signaling and diminish the systemic cytokine response induced by LPS [ 97 ].…”

Differential Transcriptomic Profiles in Canine Intestinal Organoids Following Lipopolysaccharide Stimulation

“…TAP2 and trefoil factor 1 (TFF1) upregulation in IBD enteroids and colonoids following LPS treatment could result from their ability to modulate TLR4 signaling or their anti-in ammatory properties [72][73][74] . TAP2 has been shown to inhibit TLR4 signaling and diminish the systemic cytokine response induced by LPS 72 .…”

IFNγ-dependent silencing of TFF1 during Helicobacter pylori infection

“…More recently, TFF1 has been reported to induce the formation of aggregates in which bacteria lose their spiral shape and exhibit reduced motility, suggesting that TFF1 might exert its royalsocietypublishing.org/journal/rsob Open Biol. 12: 220278 protective role by slowing down the motion of Helicobacter towards the epithelium [28].…”

“…It is also known for binding to Helicobacter , which may favour the tropism of the bacteria within the human gastric mucosa [27]. More recently, TFF1 has been reported to induce the formation of aggregates in which bacteria lose their spiral shape and exhibit reduced motility, suggesting that TFF1 might exert its protective role by slowing down the motion of Helicobacter towards the epithelium [28].…”