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Neutralizing antibodies for Helicobacter pylori urease inhibit bacterial colonization in the murine stomach in vivo.
Biomedical Research ( IF 1.2 ) Pub Date : 2019-04-16 , DOI: 10.2220/biomedres.40.87
Hikaru Takeshita 1, 2 , Eri Watanabe 1 , Yoshihiko Norose 1 , Yasuhiko Ito 2 , Hidemi Takahashi 1
Affiliation  

Helicobacter pylori (H. pylori) urease is a key protein for persistent infection of the bacteria in the stomach. Although H. pylori generally induce anti-H. pylori-specific antibodies (Abs), these Abs do not usually work for eradication or prevention of the H. pylori infection. In our previous study, we identified a linear epitope composed of 19-mer peptides termed UB-33, CHHLDKSIKEDVQFADSRI, within the large subunit of H. pylori urease. Anti-UB-33-specific Abs neutralized the enzymatic activity of H. pylori urease in vitro. In the present study, we evaluated the effect of immunization of BALB/c mice with H. pylori UB-33 peptide. After confirming the production of anti-UB-33-specific Abs, mice were challenged orally with H. pylori Sydney Strain-1 (SS-1). Mice producing anti-UB-33-specific Abs were not infected with SS-1, and the amount of SS-1 isolate in their stomach was significantly reduced. Also, the urease-negative mutant of H. pylori, HPP1801, did not colonize in the stomach, indicating that H. pylori urease was a critical element for infection of H. pylori in the gastric mucosa. Moreover, mice producing UB-33-specific Abs apparently suppressed H. pylori infection in the stomach where anti-UB-33 Abs were secreted in the gastric juice, indicating that H. pylori colonization was inhibited in the presence of anti-UB-33 Abs. In addition, the neutralization activity of sera from mice immunized with purified urease was less potent than that in the sera from mice immunized with UB-33. Furthermore, the recognition of epitope UB-33 was mediated through Toll-like receptor 2 (TLR2) on the B-1 cells using TLR2-knockout BALB/c mice in vivo. These results indicate that liner peptide UB-33 should be used for immunization to induce neutralizing Abs instead of purified H. pylori urease to prevent H. pylori infection and their colonization in the stomach.

中文翻译:

幽门螺杆菌脲酶的中和抗体可在体内抑制鼠胃细菌的定植。

幽门螺杆菌(H. pylori)尿素酶是持续感染胃中细菌的关键蛋白。尽管幽门螺杆菌通常诱导抗-H。幽门螺杆菌特异性抗体(Abs),这些抗体通常无法根除或预防幽门螺杆菌感染。在我们先前的研究中,我们在幽门螺杆菌尿素酶的大亚基中鉴定了由称为UB-33的19-聚体肽组成的线性表位,CHHLDKSIKEDVQFADSRI。抗UB-33特异性抗体在体外中和了幽门螺杆菌脲酶的酶活性。在本研究中,我们评估了用幽门螺杆菌UB-33肽免疫BALB / c小鼠的效果。确认产生抗UB-33特异性抗体后,用幽门螺杆菌Sydney Strain-1(SS-1)口服攻击小鼠。产生抗UB-33特异性抗体的小鼠未感染SS-1,并且他们的胃中SS-1分离物的数量大大减少。此外,幽门螺杆菌的脲酶阴性突变体HPP1801并未在胃中定植,这表明幽门螺杆菌脲酶是感染胃粘膜中幽门螺杆菌的关键因素。而且,产生UB-33特异性Abs的小鼠明显抑制了胃中幽门螺杆菌的感染,其中胃液中分泌了抗UB-33 Abs,这表明在存在抗UB-33的情况下幽门螺杆菌的定殖受到抑制。吸收 另外,用纯化的脲酶免疫的小鼠的血清的中和活性比用UB-33免疫的小鼠的血清的中和活性低。此外,在体内使用TLR2-敲除BALB / c小鼠,通过B-1细胞上的Toll样受体2(TLR2)介导表位UB-33的识别。
更新日期:2019-11-01
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