The TLR4-TRIF-type 1 IFN-IFN-γ pathway is crucial for gastric MALT lymphoma formation after Helicobacter suis infection

Koji Yamamoto; Yasuyuki Kondo; Shunsuke Ohnishi; Masaru Yoshida; Toshiro Sugiyama; Naoya Sakamoto

doi:10.1016/j.isci.2021.103064

The TLR4-TRIF-type 1 IFN-IFN-γ pathway is crucial for gastric MALT lymphoma formation after Helicobacter suis infection

iScience. 2021 Aug 30;24(9):103064. doi: 10.1016/j.isci.2021.103064. eCollection 2021 Sep 24.

Authors

Koji Yamamoto^{1

2}, Yasuyuki Kondo³, Shunsuke Ohnishi², Masaru Yoshida^{3

4}, Toshiro Sugiyama¹, Naoya Sakamoto²

Affiliations

¹ Research Division of Molecular Targeting Therapy and Prevention of GI Cancer, Hokkaido University Hospital, Sapporo, Hokkaido 060-8638, Japan.
² Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
³ Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan.
⁴ Division of Metabolomics Research, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan.

Abstract

Helicobacter suis, a zoonotic infection-related bacterium, can induce gastric mucosa-associated lymphoid tissue (MALT) lymphoma in humans and animals. Recently, we reported that the formation of gastric MALT lymphoma after H. suis infection is induced by interferon (IFN)-γ activation. Here, we revealed that activation of the Toll-like receptor (TLR) 4-Toll/IL-1 receptor domain-containing adapter-inducing interferon-β (TRIF) pathway after H. suis infection is associated with the production of type 1 IFNs (IFN-α, IFN-β) by gastric epithelial cells. Additionally, these type 1 IFNs interact with type 1 IFN receptors on gastric B cells, facilitating the secretion of IFN-γ and the activation of which is enhanced by positive feedback regulation in B cells. These results suggest that the TLR4-TRIF-type 1 IFN-IFN-γ pathway is crucial in the development of gastric MALT lymphoma after H. suis infection and may, therefore, represent a therapeutic target for the prevention of this condition.

Keywords: biological sciences; cancer; immunology; microbiology.