C-reactive protein is essential for innate resistance to pneumococcal infection

J. Paul Simons, Jutta M. Loeffler, Raya Al-Shawi, Stephan Ellmerich, Winston L. Hutchinson, Glenys A. Tennent, Aviva Petrie, John G. Raynes, J. Brian de Souza, Rachel A. Lawrence, Kevin D. Read, Mark B. Pepys (Lead / Corresponding author)

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    Abstract

    Summary: 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.
    Original languageEnglish
    Pages (from-to)414-420
    Number of pages7
    JournalImmunology
    Volume142
    Issue number3
    DOIs
    Publication statusPublished - Jul 2014

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    Pneumococcal Infections
    C-Reactive Protein
    Anti-Idiotypic Antibodies
    Antibodies

    Cite this

    Simons, J. P., Loeffler, J. M., Al-Shawi, R., Ellmerich, S., Hutchinson, W. L., Tennent, G. A., ... Pepys, M. B. (2014). C-reactive protein is essential for innate resistance to pneumococcal infection. Immunology, 142(3), 414-420. https://doi.org/10.1111/imm.12266
    Simons, J. Paul ; Loeffler, Jutta M. ; Al-Shawi, Raya ; Ellmerich, Stephan ; Hutchinson, Winston L. ; Tennent, Glenys A. ; Petrie, Aviva ; Raynes, John G. ; de Souza, J. Brian ; Lawrence, Rachel A. ; Read, Kevin D. ; Pepys, Mark B. / C-reactive protein is essential for innate resistance to pneumococcal infection. In: Immunology. 2014 ; Vol. 142, No. 3. pp. 414-420.
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    abstract = "Summary: 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.",
    author = "Simons, {J. Paul} and Loeffler, {Jutta M.} and Raya Al-Shawi and Stephan Ellmerich and Hutchinson, {Winston L.} and Tennent, {Glenys A.} and Aviva Petrie and Raynes, {John G.} and {de Souza}, {J. Brian} and Lawrence, {Rachel A.} and Read, {Kevin D.} and Pepys, {Mark B.}",
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    Simons, JP, Loeffler, JM, Al-Shawi, R, Ellmerich, S, Hutchinson, WL, Tennent, GA, Petrie, A, Raynes, JG, de Souza, JB, Lawrence, RA, Read, KD & Pepys, MB 2014, 'C-reactive protein is essential for innate resistance to pneumococcal infection', Immunology, vol. 142, no. 3, pp. 414-420. https://doi.org/10.1111/imm.12266

    C-reactive protein is essential for innate resistance to pneumococcal infection. / Simons, J. Paul; Loeffler, Jutta M.; Al-Shawi, Raya; Ellmerich, Stephan; Hutchinson, Winston L.; Tennent, Glenys A.; Petrie, Aviva; Raynes, John G.; de Souza, J. Brian; Lawrence, Rachel A.; Read, Kevin D.; Pepys, Mark B. (Lead / Corresponding author).

    In: Immunology, Vol. 142, No. 3, 07.2014, p. 414-420.

    Research output: Contribution to journalArticle

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    AU - Hutchinson, Winston L.

    AU - Tennent, Glenys A.

    AU - Petrie, Aviva

    AU - Raynes, John G.

    AU - de Souza, J. Brian

    AU - Lawrence, Rachel A.

    AU - Read, Kevin D.

    AU - Pepys, Mark B.

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    AB - Summary: 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.

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    Simons JP, Loeffler JM, Al-Shawi R, Ellmerich S, Hutchinson WL, Tennent GA et al. C-reactive protein is essential for innate resistance to pneumococcal infection. Immunology. 2014 Jul;142(3):414-420. https://doi.org/10.1111/imm.12266