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首页> 外文期刊>Infection and immunity >Bordetella pertussis filamentous hemagglutinin: evaluation as a protective antigen and colonization factor in a mouse respiratory infection model.
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Bordetella pertussis filamentous hemagglutinin: evaluation as a protective antigen and colonization factor in a mouse respiratory infection model.

机译：百日咳博德特氏菌丝状血凝素：在小鼠呼吸道感染模型中作为保护性抗原和定居因子的评估。

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Filamentous hemagglutinin (FHA) is a cell surface protein of Bordetella pertussis which functions as an adhesin for this organism. It is a component of many new acellular pertussis vaccines. The proposed role of FHA in immunity to pertussis is based on animal studies which have produced some conflicting results. To clarify this situation, we reexamined the protective activity of FHA in an adult mouse respiratory infection model. Four-week-old BALB/c mice were immunized with one or two doses of 4 or 8 micrograms of FHA and then aerosol challenged with B. pertussis Tohama I. In control mice receiving tetanus toxoid, the CFU in the lungs increased from 10(5) immediately following infection to greater than 10(6) by days 5 and 9 after challenge. Mice immunized with FHA by the intraperitoneal or intramuscular route had significantly reduced bacterial colonization in the lungs. A decrease in colonization of the trachea was also observed in FHA-immunized mice. Evaluation of antibody responses in these mice revealed high titers of immunoglobulin G (IgG) and IgM to FHA in sera and of IgG to FHA in lung lavage fluids. No IgA to FHA was detected. BALB/c mice were also passively immunized intravenously with either goat or rat antibodies to FHA and then aerosol challenged 24 h later, when anti-FHA antibodies were detected in the respiratory tract. Lung and tracheal colonization was markedly reduced in mice immunized with FHA-specific antibodies compared with those receiving control antibodies. In additional studies, the role of FHA in the colonization of the mouse respiratory tract was evaluated by using strain BP101, an FHA mutant of B. pertussis. FHA was important in the initial colonization of the mouse trachea, but was not required for colonization of the trachea later in the infection. FHA was not a factor in colonization of the lungs. Collectively, these experiments demonstrate (i) that systemic immunization with FHA can provide significant protection against B. pertussis infection in both the lower and upper respiratory tract of mice as defined by the lungs and trachea, respectively; (ii) that this protection is mediated primarily by serum antibodies to FHA, which transudate into respiratory secretions; and (iii) that FHA is an important upper respiratory tract colonization factor. These studies provide further evidence for the role of FHA in pertussis pathogenesis and immunity.
机译：丝状血凝素（FHA）是百日咳博德特氏菌的细胞表面蛋白，可作为该生物的粘附素。它是许多新的脱细胞百日咳疫苗的组成部分。 FHA对百日咳免疫力的拟议作用是基于动物研究，该研究产生了一些矛盾的结果。为了澄清这种情况，我们重新检查了FHA在成年小鼠呼吸道感染模型中的保护活性。用一剂或两剂4或8微克FHA免疫四周大的BALB / c小鼠，然后用百日咳博德特氏菌Tohama I进行气溶胶攻击。在接受破伤风类毒素的对照组小鼠中，肺部CFU从10增加（ 5）感染后第5天和第9天感染后立即超过10（6）。通过腹膜内或肌肉内途径用FHA免疫的小鼠的肺部细菌定植明显减少。在FHA免疫小鼠中也观察到气管定植减少。对这些小鼠中抗体反应的评估显示，血清中免疫球蛋白G（IgG）和IgM对FHA的效价高，而对肺灌洗液中IgG对FHA的效价高。未检测到FHA的IgA。当在呼吸道中检测到抗FHA抗体时，也用山羊或大鼠FHA抗体对BALB / c小鼠进行被动免疫静脉内免疫，然后在24小时后进行气雾攻击。与接受对照抗体的小鼠相比，用FHA特异性抗体免疫的小鼠的肺和气管定植明显减少。在其他研究中，通过使用菌株BP101（百日咳博德特氏菌的FHA突变体）评估了FHA在小鼠呼吸道定植中的作用。 FHA在小鼠气管的最初定居中很重要，但在感染后期在气管中定居并不是必需的。 FHA不是肺部定植的因素。总体而言，这些实验证明（i）用FHA进行全身免疫可分别针对小鼠的下呼吸道和上呼吸道，分别针对肺和气管，对百日咳博德特氏菌感染提供重要的保护; （ii）这种保护主要是由针对FHA的血清抗体介导的，该抗体会渗入呼吸道分泌物中; （iii）FHA是重要的上呼吸道定植因子。这些研究为FHA在百日咳发病机理和免疫中的作用提供了进一步的证据。

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