Binsker Ulrike, Lees John A, Hammond Alexandria J, Weiser Jeffrey N
J Clin Invest. 2020 Feb 3;130(2):927-941. doi: 10.1172/JCI132005.
Successful infection by mucosal pathogens requires overcoming the mucus barrier. To better understand this key step, we performed a survey of the interactions between human respiratory mucus and the human pathogen Streptococcus pneumoniae. Pneumococcal adherence to adult human nasal fluid was seen only by isolates expressing pilus-1. Robust binding was independent of pilus-1 adhesive properties but required Fab-dependent recognition of RrgB, the pilus shaft protein, by naturally acquired secretory IgA (sIgA). Pilus-1 binding by specific sIgA led to bacterial agglutination, but adherence required interaction of agglutinated pneumococci and entrapment in mucus particles. To test the effect of these interactions in vivo, pneumococci were preincubated with human sIgA before intranasal challenge in a mouse model of colonization. sIgA treatment resulted in rapid immune exclusion of pilus-expressing pneumococci. Our findings predict that immune exclusion would select for nonpiliated isolates in individuals who acquired RrgB-specific sIgA from prior episodes of colonization with piliated strains. Accordingly, genomic data comparing isolates carried by mothers and their children showed that mothers are less likely to be colonized with pilus-expressing strains. Our study provides a specific example of immune exclusion involving naturally acquired antibody in the human host, a major factor driving pneumococcal adaptation.
黏膜病原体的成功感染需要克服黏液屏障。为了更好地理解这一关键步骤，我们对人类呼吸道黏液与人类病原体肺炎链球菌之间的相互作用进行了一项调查。只有表达1型菌毛的分离株才能观察到肺炎球菌对成人鼻腔分泌物的黏附。强大的结合不依赖于1型菌毛的黏附特性，但需要天然获得的分泌型IgA（sIgA）对菌毛杆蛋白RrgB进行Fab依赖性识别。特定sIgA介导的1型菌毛结合导致细菌凝集，但黏附需要凝集的肺炎球菌相互作用并被困在黏液颗粒中。为了在体内测试这些相互作用的效果，在小鼠定植模型中进行鼻内攻击之前，将肺炎球菌与人sIgA预孵育。sIgA处理导致表达菌毛的肺炎球菌迅速被免疫排斥。我们的研究结果预测，在从先前感染有菌毛菌株的定植中获得RrgB特异性sIgA的个体中，免疫排斥将选择无菌毛的分离株。因此，比较母亲及其子女携带的分离株的基因组数据表明，母亲感染表达菌毛菌株的可能性较小。我们的研究提供了一个涉及人类宿主中天然获得抗体的免疫排斥的具体例子，这是驱动肺炎球菌适应性的一个主要因素。
