Concomitant Infection of S. mansoni and H. pylori Promotes Promiscuity of Antigen-Experienced Cells and Primes the Liver for a Lower Fibrotic Response

Cell Rep. 2019 Jul 2;28(1):231-244.e5. doi: 10.1016/j.celrep.2019.05.108.

Abstract

Helicobacter pylori chronically colonizes the stomach and is strongly associated with gastric cancer. Its concomitant occurrence with helminths such as schistosomes has been linked to reduced cancer incidence, presumably due to suppression of H. pylori-associated pro-inflammatory responses. However, experimental evidence in support of such a causal link or the mutual interaction of both pathogens is lacking. We investigated the effects of co-infection during the different immune phases of S. mansoni infection. Surprisingly, co-infected mice had increased H. pylori gastric colonization during the interferon gamma (IFNγ) phase of schistosome infection but reduced infiltration of T cells in the stomach due to misdirection of antigen-experienced CXCR3+ T cells to the liver. Unexpectedly, H. pylori co-infection resulted in partial protection from schistosome-induced liver damage. Here, we demonstrate that an increase in fibrosis-protective IL-13Ra2 is associated with H. pylori infection. Thus, our study strongly points to an immunological interaction of anatomically isolated pathogens, eventually resulting in altered disease pathology.

Keywords: Helicobacter pylori; Schistosoma mansoni; chronic disease; co-infection; immune misdirection; liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / immunology
  • Bone Marrow Cells / metabolism
  • Coinfection / immunology*
  • Coinfection / microbiology
  • Coinfection / parasitology
  • Cytokines / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / metabolism
  • Female
  • Gastritis / immunology
  • Gastritis / metabolism
  • Gastritis / microbiology*
  • Gastritis / parasitology
  • Helicobacter Infections / immunology*
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / pathology
  • Helicobacter pylori*
  • Humans
  • Interferon-gamma / metabolism
  • Liver / metabolism
  • Liver / microbiology
  • Liver / parasitology
  • Liver / pathology
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / microbiology*
  • Liver Cirrhosis / parasitology*
  • Liver Cirrhosis / pathology
  • Mice
  • Mice, Inbred C57BL
  • Schistosomiasis mansoni / immunology*
  • Schistosomiasis mansoni / metabolism
  • Schistosomiasis mansoni / pathology
  • Stomach / immunology
  • Stomach / microbiology
  • Stomach / parasitology
  • Stomach / pathology
  • Th1 Cells / immunology
  • Th2 Cells / immunology

Substances

  • Antigens
  • Cytokines
  • Interferon-gamma