C-reactive protein is essential for innate resistance to pneumococcal infection
Article first published online: 10 JUN 2014
© 2014 The Authors. Immunology published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 142, Issue 3, pages 414–420, July 2014
How to Cite
Paul Simons, J., Loeffler, J. M., Al-Shawi, R., Ellmerich, S., Hutchinson, W. L., Tennent, G. A., Petrie, A., Raynes, J. G., de Souza, J. B., Lawrence, R. A., Read, K. D. and Pepys, M. B. (2014), C-reactive protein is essential for innate resistance to pneumococcal infection. Immunology, 142: 414–420. doi: 10.1111/imm.12266
- Issue published online: 10 JUN 2014
- Article first published online: 10 JUN 2014
- Accepted manuscript online: 12 FEB 2014 06:05AM EST
- Manuscript Revised: 5 FEB 2014
- Manuscript Accepted: 5 FEB 2014
- Manuscript Received: 3 JAN 2014
- Medical Research Council
- Royal Free London NHS Foundation Trust
- UK National Institute for Health Research Biomedical Research Centre and Unit Funding Scheme
- anti-nuclear antibodies;
- C-reactive protein;
- host resistance;
- mouse knockout;
- pneumococcal infection
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.