Th1-mediated immunity against Helicobacter pylori can compensate for lack of Th17 cells and can protect mice in the absence of immunization

• Published in: PloS one Vol. 8; no. 7; p. e69384
• Main Authors: Ding, Hua, Nedrud, John G, Blanchard, Thomas G, Zagorski, Brandon M, Li, Guanghui, Shiu, Jessica, Xu, Jinghua, Czinn, Steven J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.07.2013; Public Library of Science (PLoS)
• Subjects: Animals; Antibodies - immunology; Bacteria; Biology; Cytokines; Enzyme-linked immunosorbent assay; Gastric cancer; Gastroenterology; Granulocytes; Health aspects; Helicobacter infections; Helicobacter Infections - immunology; Helicobacter Infections - microbiology; Helicobacter pylori; Helicobacter pylori - immunology; Helper cells; House mouse; Immune response; Immune system; Immunity; Immunity - immunology; Immunization; Immunization - methods; Infection; Infections; Inflammation; Inflammatory response; Interferon-gamma - immunology; Interleukin 12; Interleukin 17; Interleukin 23; Interleukin-12 Subunit p35 - immunology; Interleukin-23 Subunit p19 - immunology; Laboratory animals; Lymphocytes; Lymphocytes T; Medicine; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Pathology; Pediatrics; Rodents; Spleen; Stomach cancer; Studies; Th1 Cells - immunology; Th17 Cells - immunology; Therapy; Vaccination - methods; Vaccines; γ-Interferon; United States > US; Maryland; Baltimore Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0069384

Helicobacter pylori (H. pylori) infection can be significantly reduced by immunization in mice. Th17 cells play an essential role in the protective immune response. Th1 immunity has also been demonstrated to play a role in the protective immune response and can compensate in the absence of IL-17. To further address the potential of Th1 immunity, we investigated the efficacy of immunization in mice deficient in IL-23p19, a cytokine that promotes Th17 cell development. We also examined the course of Helicobacter infection in unimmunized mice treated with Th1 promoting cytokine IL-12. C57BL/6, IL-12 p35 KO, and IL-23 p19 KO mice were immunized and challenged with H. pylori. Protective immunity was evaluated by CFU determination and QPCR on gastric biopsies. Gastric and splenic IL-17 and IFNγ levels were determined by PCR or by ELISA. Balb/c mice were infected with H. felis and treated with IL-12 therapy and the resulting gastric bacterial load and inflammatory response were assessed by histologic evaluation. Vaccine induced reductions in bacterial load that were comparable to wild type mice were observed in both IL-12 p35 and IL-23 p19 KO mice. In the absence of IL-23 p19, IL-17 levels remained low but IFNγ levels increased significantly in both immunized challenged and unimmunized/challenged mice. Additionally, treatment of H. felis-infected Balb/c mice with IL-12 resulted in increased gastric inflammation and the eradication of bacteria in most mice. These data suggest that Th1 immunity can compensate for the lack of IL-23 mediated Th17 responses, and that protective Th1 immunity can be induced in the absence of immunization through cytokine therapy of the infected host.