Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
PLoS One. 2013 Jul 11;8(7):e69384. doi: 10.1371/journal.pone.0069384. Print 2013.
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.
幽门螺杆菌(H. pylori)感染可通过小鼠免疫显著减少。Th17 细胞在保护性免疫反应中发挥重要作用。Th1 免疫也被证明在保护性免疫反应中发挥作用,并可在缺乏 IL-17 的情况下发挥作用。为了进一步研究 Th1 免疫的潜力,我们研究了缺乏细胞因子 IL-23p19 的小鼠(促进 Th17 细胞发育的细胞因子)免疫接种的效果。我们还研究了在未免疫的小鼠中用促进 Th1 免疫的细胞因子 IL-12 治疗后,幽门螺杆菌感染的过程。C57BL/6、IL-12 p35 KO 和 IL-23 p19 KO 小鼠接受免疫接种并接受 H. pylori 挑战。通过 CFU 测定和胃活检的 QPCR 评估保护性免疫。通过 PCR 或 ELISA 测定胃和脾中的 IL-17 和 IFNγ 水平。用 H. felis 感染 Balb/c 小鼠,并进行 IL-12 治疗,通过组织学评估评估胃内细菌负荷和炎症反应。在缺乏 IL-23 p19 的情况下,在免疫接种和未免疫接种/挑战的小鼠中,观察到与野生型小鼠相当的细菌负荷减少。此外,用 IL-12 治疗 H. felis 感染的 Balb/c 小鼠导致胃炎症增加,大多数小鼠中的细菌被消除。这些数据表明,Th1 免疫可以补偿缺乏 IL-23 介导的 Th17 反应,并且可以通过感染宿主的细胞因子治疗在没有免疫接种的情况下诱导保护性 Th1 免疫。