title: C-reactive protein is essential for innate resistance to pneumococcal infection.
abstract: 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.
authors.affiliation: Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, University College London, London, UK.
authors.forename: J Paul
authors.initials: JP
authors.lastname: Simons
authors.forename: Jutta M
authors.initials: JM
authors.lastname: Loeffler
authors.forename: Raya
authors.initials: R
authors.lastname: Al-Shawi
authors.forename: Stephan
authors.initials: S
authors.lastname: Ellmerich
authors.forename: Winston L
authors.initials: WL
authors.lastname: Hutchinson
authors.forename: Glenys A
authors.initials: GA
authors.lastname: Tennent
authors.forename: Aviva
authors.initials: A
authors.lastname: Petrie
authors.forename: John G
authors.initials: JG
authors.lastname: Raynes
authors.forename: J Brian
authors.initials: JB
authors.lastname: de Souza
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Lawrence
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Read
authors.forename: Mark B
authors.initials: MB
authors.lastname: Pepys
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011008:Pneumococcal Infections / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D002097:C-Reactive Protein
keywords: C-reactive protein; anti-nuclear antibodies; host resistance; mouse knockout; pneumococcal infection