Pishko Elizabeth J, Betting David J, Hutter Christina S, Harvill Eric T
Department of Veterinary Science, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Infect Immun. 2003 Sep;71(9):4936-42. doi: 10.1128/IAI.71.9.4936-4942.2003.
In order to initially colonize a host, bacteria must avoid various components of the innate immune system, one of which is complement. The genus Bordetella includes three closely related species that differ in their ability to resist complement-mediated killing. Bordetella parapertussis and Bordetella bronchiseptica resist killing in naïve serum, a characteristic that may aid in efficient respiratory tract colonization and has been attributed to expression of O antigen. Bordetella pertussis lacks O antigen and is sensitive to naïve serum in vitro, yet it also efficiently colonizes the respiratory tract. Based on these observations, we hypothesized that B. pertussis may have an alternate mechanism to resist complement in vivo. While a number of reports on serum sensitivity of the bordetellae have been published, we show here that serum concentration and growth conditions can greatly alter the observed level of sensitivity to complement and that all but one strain of B. pertussis observed were sensitive to some level of naïve serum in vitro, particularly when there was excess complement. However, B. pertussis rapidly acquires increased resistance in vivo to naïve serum that is specific to the alternative pathway. Resistance is not efficiently acquired by B. parapertussis and B. bronchiseptica mutants lacking O antigen. This B. pertussis-specific mechanism of complement resistance does not appear to be dependent on either brkA or other genes expressed specifically in the Bvg(+) phase. This in vivo acquisition of alternative pathway resistance suggests that there is a novel O antigen-independent method by which B. pertussis evades complement-mediated killing.
为了最初定殖于宿主,细菌必须避开天然免疫系统的各种成分,补体就是其中之一。博德特氏菌属包括三个密切相关的种,它们抵抗补体介导杀伤的能力有所不同。副百日咳博德特氏菌和支气管败血博德特氏菌能在未免疫血清中抵抗杀伤,这一特性可能有助于在呼吸道有效定殖,且这归因于O抗原的表达。百日咳博德特氏菌缺乏O抗原,在体外对未免疫血清敏感,但它也能有效地定殖于呼吸道。基于这些观察结果,我们推测百日咳博德特氏菌可能有另一种在体内抵抗补体的机制。虽然已经发表了许多关于博德特氏菌血清敏感性的报告,但我们在此表明,血清浓度和生长条件可极大地改变观察到的对补体的敏感水平,并且观察到的所有百日咳博德特氏菌菌株中,除一株外,在体外对某种水平的未免疫血清均敏感,尤其是在有过量补体的情况下。然而,百日咳博德特氏菌在体内能迅速获得对未免疫血清的增强抗性,这种抗性是替代途径特有的。缺乏O抗原的副百日咳博德特氏菌和支气管败血博德特氏菌突变体不能有效地获得抗性。百日咳博德特氏菌这种特异性的补体抗性机制似乎不依赖于brkA或其他在Bvg(+)期特异性表达的基因。这种在体内获得替代途径抗性表明,存在一种新的不依赖O抗原的方法,百日咳博德特氏菌可借此逃避补体介导的杀伤。