Role of Toll-like receptors in Helicobacter pylori infection and immunity

Abstract

The gram-negative bacterium Helicobacter pylori (H. pylori) infects the stomachs of approximately half of the world’s population. Although infection induces an immune response that contributes to chronic gastric inflammation, the response is not sufficient to eliminate the bacterium. H. pylori infection causes peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Disease outcome is linked to the severity of the host inflammatory response. Gastric epithelial cells represent the first line of innate immune defence against H. pylori, and respond to infection by initiating numerous cell signalling cascades, resulting in cytokine induction and the subsequent recruitment of inflammatory cells to the gastric mucosa. Pathogen recognition receptors of the Toll-like receptor (TLR) family mediate many of these cell signalling events. This review discusses recent findings on the role of various TLRs in the recognition of H. pylori in distinct cell types, describes the TLRs responsible for the recognition of individual H. pylori components and outlines the influence of innate immune activation on the subsequent development of the adaptive immune response. The mechanistic identification of host mediators of H. pylori-induced pathogenesis has the potential to reveal drug targets and opportunities for therapeutic intervention or prevention of H. pylori-associated disease by means of vaccines or immunomodulatory therapy.

Keywords: Helicobacter pylori; Toll-like receptor; Gastric epithelium; Monocyte; Macrophage; Dendritic cell; Cytokine; Lipopolysaccharide

Core tip: Eradication rates for Helicobacter pylori (H. pylori) infection have fallen. The development of therapeutic alternatives to antibiotics, such as immunomodulatory therapy and vaccines requires a clearer understanding of host-pathogen interactions. As Toll-like receptors are intimately involved in the regulation of inflammation in response to H. pylori and represent key activators of adaptive immunity, they represent a target for therapeutic manipulation. Elucidating innate immune signals triggered by H. pylori will provide an understanding of how the balance between pro-inflammatory and anti-inflammatory signals fine-tunes the response to infection and insight into how the immune response may be manipulated therapeutically to successfully eradicate the bacterium.