Helicobacter pyloriChemotaxis Modulates Inflammation and Bacterium-Gastric Epithelium Interactions in Infected Mice

Abstract

The ulcer-causing pathogen Helicobacter pylori uses directed motility, or chemotaxis, to both colonize the stomach and promote disease development. Previous work showed that mutants lacking the TlpB chemoreceptor, one of the receptors predicted to drive chemotaxis, led to less inflammation in the gerbil stomach than did the wild type. Here we expanded these findings and examined the effects on inflammation of completely nonchemotactic mutants and mutants lacking each chemoreceptor. Of note, all mutants colonized mice to the same levels as did wild-type H. pylori. Infection by completely nonchemotactic mutants (cheW or cheY) resulted in significantly less inflammation after both 3 and 6 months of infection. Mutants lacking either the TlpA or TlpB H. pylori chemotaxis receptors also had alterations in inflammation severity, while mutants lacking either of the other two chemoreceptors (TlpC and HylB) behaved like the wild type. Fully nonchemotactic and chemoreceptor mutants adhered to cultured gastric epithelial cells and caused cellular release of the chemokine interleukin-8 in vitro similar to the release caused by the wild type. The situation appeared to be different in the stomach. Using silver-stained histological sections, we found that nonchemotactic cheY or cheW mutants were less likely than the wild type to be intimately associated with the cells of the gastric mucosa, although there was not a strict correlation between intimate association and inflammation. Because others have shown that in vivo adherence promotes inflammation, we propose a model in which H. pylori uses chemotaxis to guide it to a productive interaction with the stomach epithelium.

Energy Taxis Drives Campylobacter jejuni toward the Most Favorable Conditions for Growth

“…Multiple studies of Tlp proteins from the closely related organism H. pylori have demonstrated the functions of these proteins to be complex and not readily apparent when analyzed under in vitro conditions. Thus, several H. pylori tlp mutants have shown contradictory or host-dependent results in terms of colonization potential (3,12,32,39,49). However, the general picture from H. pylori, as well as C. jejuni, is that the Tlp proteins contribute to the physiological fitness of these organisms when facing the challenges encountered during host colonization.…”

“…Thus, tlp1, tlp3, and docB could potentially encode proteins directly involved in host interaction. (29,49). However, knowledge regarding the environmental signals promoting the chemotactic orientation and the sensing of these signals is limited.…”

Bacterial chemotaxis modulates host cell apoptosis to establish a T-helper cell, type 17 (Th17)-dominant immune response in Helicobacter pylori infection

“…As stated above, Che − H. pylori cause milder inflammation than do wild-type infections after 3-6 mo of colonization (4). To determine whether bacterial chemotaxis affected inflammation earlier, we examined inflammation at the earliest time inflammation was detectable, 2 mo after inoculation.…”

“…In mouse models, these mutants have a marginal colonization defect (4-6) but induce less overall chronic inflammation (4). Specifically, Che − mutants localize far from the epithelial surface and do not colonize the gastric glands robustly (4,6), suggesting that chemotaxis-driven contact with epithelial cells, resident dendritic cells, or monocytes promotes the inflammatory response to H. pylori.…”

“…Inflammation is promoted by both host factors (2) and H. pylori factors, such as the proteins cytotoxin associated gene A (CagA) (1, 2) and vacuolating cytotoxin A (VacA) (1,3) and bacterial chemotaxis (4). Chemotaxis is the bacterial ability to move toward beneficial environmental signals and away from harmful ones.…”