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
Affiliations
Koji Yamamoto
Research Division of Molecular Targeting Therapy and Prevention of GI Cancer, Hokkaido University Hospital, Sapporo, Hokkaido 060-8638, Japan; Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan; Corresponding author
Yasuyuki Kondo
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
Shunsuke Ohnishi
Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan
Masaru Yoshida
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan; Division of Metabolomics Research, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
Toshiro Sugiyama
Research Division of Molecular Targeting Therapy and Prevention of GI Cancer, Hokkaido University Hospital, Sapporo, Hokkaido 060-8638, Japan
Naoya Sakamoto
Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan
Summary: 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.
