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首页> 外文期刊>mSphere >Intravaginal Administration of Interleukin 12 during Genital Gonococcal Infection in Mice Induces Immunity to Heterologous Strains of Neisseria gonorrhoeae
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Intravaginal Administration of Interleukin 12 during Genital Gonococcal Infection in Mice Induces Immunity to Heterologous Strains of Neisseria gonorrhoeae

机译：小鼠生殖器淋球菌感染过程中的白细胞介素12的阴道内注射可诱导淋病奈瑟氏球菌异源菌免疫

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It has previously been shown that genital tract infection with Neisseria gonorrhoeae in mice does not induce a state of protective immunity against reinfection but instead suppresses the development of adaptive immune responses against N. gonorrhoeae dependent on transforming growth factor beta (TGF-β) and interleukin 10 (IL-10). Intravaginal administration during gonococcal infection of IL-12 encapsulated in biodegradable microspheres (IL-12/ms) reverses the immunosuppression and promotes the production of gamma interferon (IFN-γ) and of specific antibodies in serum and genital secretions and accelerates clearance of the infection. In this study, microspheres were shown to remain largely within the genital tract lumen and to release IL-12 over the course of 4 days. Antigonococcal IgA and IgG antibodies induced by IL-12/ms treatment reacted with antigenically different strains of N. gonorrhoeae and led to resistance to reinfection with heterologous and homologous strains. Immune resistance to reinfection persisted for at least 6 months after clearance of the primary infection. Experiments performed with immunodeficient strains of mice lacking either IFN-γ or B cells demonstrated that both IFN-γ and B cells were necessary for the IL-12-induced generation of immune responses to N. gonorrhoeae and the resulting accelerated clearance of the infection. It is therefore concluded that intravaginally administered IL-12/ms achieves its effect by the sustained release of IL-12 that promotes Th1-driven adaptive immune responses, including the production of specific antigonococcal antibodies that cross-react with multiple strains of N. gonorrhoeae . IL-12-enhanced immunity to N. gonorrhoeae can be recalled against reinfection after prolonged intervals and is dependent upon both IFN-γ and antibody production by B cells. IMPORTANCE Genital infection with Neisseria gonorrhoeae (gonorrhea) is a significant cause of reproductive tract morbidity in women, leading to pelvic inflammatory disease, tubal factor infertility, and increased risk for ectopic pregnancy. WHO estimates that 78 million new infections occur annually worldwide. In the United States, >350,000 cases are reported annually, but the true incidence is probably >800,000 cases/year. Increasing resistance to currently available antibiotics raises concern that gonorrhea might become untreatable. Infection does not induce a state of immune protection against reinfection. Previous studies have shown that N. gonorrhoeae suppresses the development of adaptive immune responses by mechanisms dependent on the regulatory cytokines TGF-β and IL-10. This study shows that intravaginal treatment of gonococcal infection in female mice with microencapsulated IL-12 induces persisting anamnestic immunity against reinfection with N. gonorrhoeae , even of antigenically diverse strains, dependent on T-cell production of IFN-γ and B-cell production of antibodies.
机译：以前已经证明，小鼠淋病奈瑟菌的生殖道感染不会诱导针对再感染的保护性免疫状态，而是抑制依赖于转化生长因子β（TGF-β）和白介素的淋病奈瑟氏球菌的适应性免疫反应的发展。 10（IL-10）。淋球菌感染封装在可生物降解微球中的IL-12（IL-12 / ms）期间进行阴道内给药可逆转免疫抑制作用，并促进血清和生殖器分泌物中的γ-干扰素（IFN-γ）和特定抗体的产生，并加速感染的清除。在这项研究中，显示微球在很大程度上保留在生殖道管腔内，并在4天的过程中释放IL-12。 IL-12 / ms处理诱导的抗淋球菌IgA和IgG抗体与淋病奈瑟氏球菌的抗原性不同菌株发生反应，并导致对异源和同源菌株的再感染产生抗性。清除原发感染后，对再感染的免疫抵抗至少持续了6个月。对缺乏IFN-γ或B细胞的免疫缺陷型小鼠进行的实验表明，IFN-γ和B细胞对于IL-12诱导的淋病奈瑟菌免疫应答的产生和感染的加速清除都是必需的。因此得出结论，阴道内给药的IL-12 / ms通过持续释放促进Th1驱动的适应性免疫应答的IL-12达到其效果，包括产生与多种淋病奈瑟菌交叉反应的特异性抗性淋球菌抗体。 。间隔较长时间后，可以唤起针对淋病奈瑟菌的IL-12增强免疫力，以防再感染，并且依赖于IFN-γ和B细胞产生的抗体。重要性淋病奈瑟氏菌（淋病）的生殖器感染是女性生殖道发病的重要原因，导致盆腔炎，输卵管不育症和异位妊娠的风险增加。世卫组织估计，全世界每年有7800万新感染。在美国，每年报告> 350,000例，但实际发病率可能是> 800,000例/年。对目前可用抗生素的耐药性增加，引起人们对淋病可能变得无法治愈的担忧。感染不会引起针对再感染的免疫保护状态。先前的研究表明淋病奈瑟氏球菌通过依赖于调节性细胞因子TGF-β和IL-10的机制抑制适应性免疫反应的发展。这项研究表明，用微囊化IL-12阴道处理雌性小鼠淋球菌感染可诱导持续的记忆力抵抗淋病奈瑟菌再感染，即使是抗原性多样的菌株，也依赖于T细胞产生的IFN-γ和B细胞产生的淋巴球菌。抗体。

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