Minimization of bacterial size allows for complement evasion and is overcome by the agglutinating effect of antibody.

Minimization of bacterial size allows for complement evasion and is overcome by the agglutinating effect of antibody.
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DOI:
10.1016/j.chom.2011.09.009
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发表时间:
2011-11-17
影响因子:
30.3
通讯作者:
Weiser JN
Weiser JN
中科院分区:
医学1区
文献类型:
--
作者:
Dalia AB;Weiser JN

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补体系统通过直接溶解病原体或通过促进吞噬细胞吸收病原体来发挥作用,对于控制许多微生物感染至关重要。在这里,我们表明,在肺炎链球菌,增加细菌链长度敏感这种病原体补体沉积和随后的人体中性粒细胞的吸收。与此一致,我们表明,最小化链长度提供了一个竞争优势,在体内的系统性感染模型中的野生型细菌。研究宿主如何克服这种毒力策略,我们发现抗体促进补体依赖性调理吞噬细胞杀死肺炎链球菌和流感嗜血杆菌的裂解,而不依赖于Fc介导的效应子功能。与抗体的凝集作用一致,F(ab′)2能促进抗体的凝集作用,而Fab不能。因此,增加病原体大小,无论是通过细胞形态的自然变化还是通过抗体介导的凝集,都会促进补体依赖性杀伤。这些观察结果对于细胞大小和形态如何影响致病微生物的毒力具有广泛的意义。
The complement system, which functions by lysing pathogens directly or by promoting their uptake by phagocytes, is critical for controlling many microbial infections. Here we show that in Streptococcus pneumoniae, increasing bacterial chain length sensitizes this pathogen to complement deposition and subsequent uptake by human neutrophils. Consistent with this, we show that minimizing chain length provides wild-type bacteria with a competitive advantage in vivo in a model of systemic infection. Investigating how the host overcomes this virulence strategy, we find that antibody promotes complement-dependent opsonophagocytic killing of Streptococcus pneumoniae and lysis of Haemophilus influenzae independent of Fc-mediated effector functions. Consistent with the agglutinating effect of antibody, F(ab′)2 but not Fab could promote this effect. Therefore, increasing pathogen size, whether by natural changes in cellular morphology or via antibody-mediated agglutination, promotes complement-dependent killing. These observations have broad implications for how cell size and morphology can affect virulence among pathogenic microbes.
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