Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, University College London, London, UK.
Immunology. 2014 Jul;142(3):414-20. doi: 10.1111/imm.12266.
No deficiency of human C-reactive protein (CRP), or even structural polymorphism of the protein, has yet been reported so its physiological role is not known. Here we show for the first time that CRP-deficient mice are remarkably susceptible to Streptococcus pneumoniae infection and are protected by reconstitution with isolated pure human CRP, or by anti-pneumococcal antibodies. Autologous mouse CRP is evidently essential for innate resistance to pneumococcal infection before antibodies are produced. Our findings are consistent with the significant association between clinical pneumococcal infection and non-coding human CRP gene polymorphisms which affect CRP expression. Deficiency or loss of function variation in CRP may therefore be lethal at the first early-life encounter with this ubiquitous virulent pathogen, explaining the invariant presence and structure of CRP in human adults.
尚未有人类 C 反应蛋白（CRP）缺乏或甚至该蛋白结构多态性的报道，因此其生理作用尚不清楚。在这里，我们首次表明，CRP 缺陷型小鼠对肺炎链球菌感染极为敏感，并可通过用分离的纯人 CRP 或抗肺炎球菌抗体进行重建而得到保护。在产生抗体之前，自体小鼠 CRP 显然对肺炎球菌感染的先天抵抗力是必需的。我们的研究结果与临床肺炎球菌感染与影响 CRP 表达的非编码人 CRP 基因多态性之间的显著相关性一致。因此，CRP 的缺乏或功能丧失变异在首次遇到这种普遍存在的毒力病原体时可能是致命的，这解释了 CRP 在人类成年期的不变存在和结构。
