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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 \u03bcg of CRP and 10<jats:sup>7<\/jats:sup>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 \u03bcg of CRP and 5 \u00d7 10<jats:sup>7<\/jats:sup>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 \u03bcg of CRP and 10<jats:sup>7<\/jats:sup>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.<\/jats:p>","DOI":"10.1128\/iai.03058-14","type":"journal-article","created":{"date-parts":[[2015,2,18]],"date-time":"2015-02-18T08:16:15Z","timestamp":1424247375000},"page":"1845-1852","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["C-Reactive Protein Protects Mice against Pneumococcal Infection via Both Phosphocholine-Dependent and Phosphocholine-Independent Mechanisms"],"prefix":"10.1128","volume":"83","author":[{"given":"Toh B.","family":"Gang","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, East Tennessee State University, Johnson City, Tennessee, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory A.","family":"Hanley","sequence":"additional","affiliation":[{"name":"Division of Laboratory Animal Resources, East Tennessee State University, Johnson City, Tennessee, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alok","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, East Tennessee State University, Johnson City, Tennessee, USA"},{"name":"Center for Inflammation, Infectious Disease and Immunity, James H. 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