New Model Allows Researchers to Study Immune Response to Bacteria that Cause Peptic Ulcers

Researchers have developed a pig model that mimics the human immune response to H. pylori infection, enabling them to better predict the progression and outcomes of infection.

The authors of “Helicobacter pylori Infection in a Pig Model Is Dominated by Th1 and Cytotoxic CD8+ T Cell Responses,” published in Infection and Immunity, have developed a model using pigs to study the immunomodulatory response to H. pylori, which is the leading cause of peptic ulcer in humans.

According to the authors, pigs inoculated with one of two strains of H. pylori were monitored for phenotypic and functional changes in peripheral blood mononuclear cell (PBMC) populations, mucosal immune responses, and bacterial loads for two months post-infection. They reported that infection with both strains “elicited a Th1 response characterized by increased percentages of CD4+Tbet+ cells and elevated gamma interferon (IFN-γ) mRNA in PBMCs.” They also found that a “subset of CD8+ T cells expressing Tbet and CD16” increased following H. pylori infection.

Investigators also observed “a significant increase in perforin and granzyme mRNA expression” in the PBMCs of the infected animals, indicating “a predominant cytotoxic immune response.” They reported that “Infiltration of B cells, myeloid cells, T cells expressing Treg- and Th17-associated transcription factors, and cytotoxic T cells was found in the gastric lamina propria of both infected groups.”

H. pylori

Based on these results, they concluded that “novel pig model of infection closely mimics human gastric pathology and presents a suitable avenue for studying effector and regulatory responses toward described in humans.”

A press release from the Virginia Bioinformatics Institute (VBI) at Virginia Tech accompanying publication of the article noted that the increase in cytotoxic T cells seen in the pig model “mirrors the recent findings in human clinical studies,” in which researchers have found “higher numbers of cytotoxic T cells in patients with H. pylori-associated gastritis, indicating that these cells may contribute to the development of gastric lesions.”

In the release, senior author Dr. Raquel Hontecillas, Co-Director of NIMML and the Center for Modeling Immunity to Enteric Pathogens, said, “Pigs have greater anatomic, physiologic and immunologic similarities to humans than mice, the main animal model used in biomedical research. The results from our new pig model closely mimic what has been reported in clinical settings, which will allow us to comprehensively and systematically investigate human immune responses to H. pylori.”