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

Abstract

<i>Helicobacter pylori</i> colonization and persistence could precede gastric adenocarcinoma. Elucidating immune recognition strategies of <i>H. pylori</i> 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 <i>H. pylori</i>. Human THP-1 monocytic cells were infected with <i>H. pylori</i>, and the expression levels of human Toll-like receptors (TLRs) were examined. The roles of TLR7 and TLR8 in response to <i>H. pylori</i> 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 <i>H. pylori</i> J99 or SS1 strains. <i>H. pylori</i> infection-mediated IFN-<i>α</i> and IFN-<i>β</i> transactivation was significantly abrogated by the TLR7/8 (but not TLR7) antagonist. Additionally, TLR7/8 antagonist treatment reduced <i>H. pylori</i> infection-mediated phosphorylation of interferon regulatory factor 7 (IRF7). Our study suggests a novel role of TLR8 signaling in host immunity against <i>H. pylori</i> through sensing live bacteria to elicit the production of type I interferon.