Gang Toh B, Hanley Gregory A, Agrawal Alok
Department of Biomedical Sciences, East Tennessee State University, Johnson City, Tennessee, USA.
Division of Laboratory Animal Resources, East Tennessee State University, Johnson City, Tennessee, USA.
Infect Immun. 2015 May;83(5):1845-52. doi: 10.1128/IAI.03058-14. Epub 2015 Feb 17.
The mechanism of action of C-reactive protein (CRP) in protecting mice against lethal Streptococcus pneumoniae infection is unknown. The involvement of the phosphocholine (PCh)-binding property of CRP in its antipneumococcal function previously has been explored twice, with conflicting results. In this study, using three different intravenous sepsis mouse models, we investigated the role of the PCh-binding property of CRP by employing a CRP mutant incapable of binding to PCh. The ability of wild-type CRP to protect mice against infection was found to differ in the three models; the protective ability of wild-type CRP decreased when the severity of infection was increased, as determined by measuring mortality and bacteremia. In the first animal model, in which we used 25 μg of CRP and 10(7) CFU of pneumococci, both wild-type and mutant CRP protected mice against infection, suggesting that the protection was independent of the PCh-binding activity of CRP. In the second model, in which we used 25 μg of CRP and 5 × 10(7) CFU of pneumococci, mutant CRP was not protective while wild-type CRP was, suggesting that the protection was dependent on the PCh-binding activity of CRP. In the third model, in which we used 150 μg of CRP and 10(7) CFU of pneumococci, mutant CRP was as protective as wild-type CRP, again indicating that the protection was independent of the PCh-binding activity of CRP. We conclude that both PCh-dependent and PCh-independent mechanisms are involved in the CRP-mediated decrease in bacteremia and the resulting protection of mice against pneumococcal infection.
C反应蛋白（CRP）保护小鼠免受致死性肺炎链球菌感染的作用机制尚不清楚。此前曾两次探讨CRP的磷酸胆碱（PCh）结合特性在其抗肺炎球菌功能中的作用，结果相互矛盾。在本研究中，我们使用三种不同的静脉脓毒症小鼠模型，通过采用一种无法与PCh结合的CRP突变体，研究了CRP的PCh结合特性的作用。野生型CRP保护小鼠免受感染的能力在三种模型中有所不同；通过测量死亡率和菌血症确定，当感染严重程度增加时，野生型CRP的保护能力下降。在第一个动物模型中，我们使用25μg CRP和10⁷CFU肺炎球菌，野生型和突变型CRP均能保护小鼠免受感染，这表明这种保护与CRP的PCh结合活性无关。在第二个模型中，我们使用25μg CRP和5×10⁷CFU肺炎球菌，突变型CRP没有保护作用，而野生型CRP有保护作用，这表明这种保护依赖于CRP的PCh结合活性。在第三个模型中，我们使用150μg CRP和10⁷CFU肺炎球菌，突变型CRP与野生型CRP的保护作用相同，再次表明这种保护与CRP的PCh结合活性无关。我们得出结论，PCh依赖性和PCh非依赖性机制均参与了CRP介导的菌血症减少以及由此产生的对小鼠肺炎球菌感染的保护作用。
