Helicobacter pylori Infection Elicits Type I Interferon Response in Human Monocytes via Toll-Like Receptor 8 Signaling

Abstract

Helicobacter pylori colonization and persistence could precede gastric adenocarcinoma. Elucidating immune recognition strategies of H. pylori is therefore imperative to curb chronic persistence in the human host. Toll-like receptor 7 (TLR7) and TLR8 are widely known as viral single-stranded RNA (ssRNA) sensors yet less studied in the bacteria context. Here, we investigated the involvement of these receptors in the immunity to H. pylori. Human THP-1 monocytic cells were infected with H. pylori, and the expression levels of human Toll-like receptors (TLRs) were examined. The roles of TLR7 and TLR8 in response to H. pylori infection were further investigated using receptor antagonists. Among all TLR transcripts examined, TLR8 exhibited the most prominent upregulation, followed by TLR7 in the THP-1 cells infected with H. pylori J99 or SS1 strains. H. pylori infection-mediated IFN-α and IFN-β transactivation was significantly abrogated by the TLR7/8 (but not TLR7) antagonist. Additionally, TLR7/8 antagonist treatment reduced H. pylori infection-mediated phosphorylation of interferon regulatory factor 7 (IRF7). Our study suggests a novel role of TLR8 signaling in host immunity against H. pylori through sensing live bacteria to elicit the production of type I interferon.

Association between dietary zinc intake and Helicobacter pylori seropositivity in US adults: National Health and Nutrition Examination Survey

“…Recent studies have revealed a significant correlation between zinc status and Toll-like receptors in the body, which could impact infection and immune function in children ( 41 ). Moreover, Toll-like receptors play a crucial role in Helicobacter pylori infection ( 42 ). As part of the innate immune system, Toll-like receptors act as the first line of defense against bacterial invasion.…”

Recent Advances on Small-Molecule Antagonists Targeting TLR7

“…TLR7 is also implicated in other infection diseases, such as Pseudomonas aeruginosa pneumonia or Helicobacter pylori infection, and TLR7 or TLR7/8 antagonist might play a positive role in bacterial recognition and treatment [ 85 , 86 , 87 ].…”

IRF7: role and regulation in immunity and autoimmunity

“…The phosphorylation of IRF7 is linked to PRR pathways. TLR7/8 antagonists reduce Helicobacter pylori infection-mediated IRF7 phosphorylation ( 51 ). Kinases such as IKKϵ, TBK1, IRAK1 and IKKα are responsible for the phosphorylation of IRF7 in a cell type-specific manner ( 52 , 53 ).…”