Journal Article

TLR2, TLR4 and TLR10 Shape the Cytokine and Chemokine Release of H. pylori-Infected Human DCs

Horejs-Hoeck, Jutta, Wessler, Silja, Neuper, Theresa, Posselt, Gernot, Sarajlic, Muamera, Frauenlob, Tobias

2020

Overview

Helicobacter pylori (H. pylori) is a stomach pathogen that persistently colonizes the gastric mucosa, often leading to chronic inflammation and gastric pathologies. Although infection with H. pylori is the primary risk factor for gastric cancer, the underlying mechanisms of pathogen persistence and consequential chronic inflammation are still not well understood. Conventional dendritic cells (cDCs), which are among the first immune cells to encounter H. pylori in the gastric lining, and the cytokines and chemokines they secrete, contribute to both acute and chronic inflammation. Therefore, this study aimed to unravel the contributions of specific signaling pathways within human CD1c+ cDCs (cDC2s) to the composition of secreted cytokines and chemokines in H. pylori infection. Here, we show that the type IV secretion system (T4SS) plays only a minor role in H. pylori-induced activation of cDC2s. In contrast, Toll-like receptor 4 (TLR4) signaling drives the secretion of inflammatory mediators, including IL-12 and IL-18, while signaling via TLR10 attenuates the release of IL-1β and other inflammatory cytokines upon H. pylori infection. The TLR2 pathway significantly blocks the release of CXCL1 and CXCL8, while it promotes the secretion of TNFα and GM-CSF. Taken together, these results highlight how specific TLR-signaling pathways in human cDC2s shape the H. pylori-induced cytokine and chemokine milieu, which plays a pivotal role in the onset of an effective immune response.

• Publisher: MDPI
• Subject: Antigens, CD1 - metabolism / Chemokines - metabolism / Communication / Cytokines - metabolism / Dendritic Cells - metabolism / Dendritic Cells - microbiology / Gastric Mucosa - metabolism / Helicobacter Infections - metabolism / Helicobacter pylori / Humans / Inflammation / Inflammation Mediators - metabolism / Leukocytes, Mononuclear - cytology / Signal Transduction / Stomach Neoplasms - microbiology / Toll-Like Receptor 10 - metabolism / Toll-Like Receptor 2 - metabolism / Toll-Like Receptor 4 - metabolism