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首页> 外文期刊>Infection and immunity >Chlamydial Protease-Like Activity Factor Induces Protective Immunity against Genital Chlamydial Infection in Transgenic Mice That Express the Human HLA-DR4 Allele
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Chlamydial Protease-Like Activity Factor Induces Protective Immunity against Genital Chlamydial Infection in Transgenic Mice That Express the Human HLA-DR4 Allele

机译：衣原体蛋白酶样活性因子诱导表达人类HLA-DR4等位基因的转基因小鼠生殖道衣原体感染的保护性免疫。

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There is no licensed vaccine available against Chlamydia trachomatis, the leading cause of bacterial sexually transmitted disease. We have found that intranasal immunization with recombinant chlamydial protease-like activity factor (CPAF) induces CD4+ T-cell- and gamma interferon (IFN-γ)-dependent protective immunity against murine genital chlamydial infection, thus making CPAF a viable vaccine candidate for further characterization. HLA-DR4 is the predominant allele involved in chlamydial antigen presentation to CD4+ T cells in humans. We used engineered mice that lack endogenous major histocompatibility complex class II (MHC-II) alleles but express a human HLA allele (HLA-DR4 transgenic [tg] mice) to examine primary immune and CPAF-mediated responses against genital Chlamydia muridarum challenge. Upon primary bacterial exposure, HLA-DR4 tg mice developed Chlamydia-specific IFN-γ and antibody production and resolved the infection within 30 days, similar to challenged conventional C57BL/6 animals. Moreover, C. muridarum-challenged HLA-DR4 tg mice exhibited CPAF-specific antibody and IFN-γ production. Upon CPAF-plus-interleukin-12 (IL-12) vaccination, HLA-DR4 tg animals exhibited robust CPAF-specific IFN-γ production and elevated titers of anti-CPAF total antibody and immunoglobulin G2a (IgG2a) and lower titers of IgG2b and IgG1 antibodies. HLA-DR4 tg and C57BL/6 mice vaccinated with CPAF plus IL-12 resolved the primary genital chlamydial infection significantly earlier than mock-immunized animals, whereas similarly vaccinated MHC class II-deficient mice displayed minimal antigen-specific immune responses and failed to resolve the infection even at 30 days postchallenge. Together, these results demonstrate the importance of human HLA-DR4 molecules in the recognition and presentation of CPAF epitopes, leading to the generation of protective antichlamydial immunity and making these mice a valuable model for mapping HLA-DR4-restricted chlamydial epitopes.
机译：目前尚无针对沙眼衣原体的细菌的许可疫苗，沙眼衣原体是细菌性传播疾病的主要原因。我们已经发现，用重组衣原体蛋白酶样活性因子（CPAF）进行鼻内免疫可诱导CD4 + T细胞和γ干扰素（IFN-γ）依赖性的针对鼠源生殖器衣原体感染的保护性免疫，从而使CPAF成为可行疫苗的进一步表征。 HLA-DR4是衣原体抗原呈递给人CD4 + T细胞的主要等位基因。我们使用缺乏内源性主要组织相容性复合体II类（MHC-II）等位基因但表达人类HLA等位基因（HLA-DR4转基因[tg]小鼠）的工程小鼠来检查针对生殖器 muridarum的主要免疫和CPAF介导的反应挑战。初次暴露于细菌后，HLA-DR4 tg小鼠出现了<衣原体特异的IFN-γ和抗体产生，并在30天之内解决了感染，类似于受攻击的常规C57BL / 6动物。此外， C。 muridarum 攻击的HLA-DR4 tg小鼠表现出CPAF特异性抗体和IFN-γ产生。在进行CPAF加白介素12（IL-12）疫苗接种后，HLA-DR4 tg动物表现出强劲的CPAF特异性IFN-γ产生，抗CPAF总抗体和免疫球蛋白G2a（IgG2a）的滴度升高，IgG2b和IgG1抗体。接种CPAF和IL-12的HLA-DR4 tg和C57BL / 6小鼠比模拟免疫的动物早得多地解决了原发性生殖道衣原体感染，而同样接种MHC II类缺陷的小鼠显示出最小的抗原特异性免疫反应，但未能解决甚至在攻击后30天感染。总之，这些结果证明了人类HLA-DR4分子在CPAF表位的识别和呈现中的重要性，从而导致保护性抗衣原体免疫的产生，并使这些小鼠成为定位HLA-DR4限制性衣原体表位的有价值的模型。

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