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C-Reactive Protein Enhances Immunity to Streptococcus pneumoniae by Targeting Uptake to FcR on Dendritic Cells¹

Deirdre Thomas-Rudolph^*, Terry W. Du Clos^,, Clifford M. Snapper and Carolyn Mold^2,*

^* Department of Molecular Genetics and Microbiology and Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131; Department of Veterans Affairs Medical Center, Albuquerque, NM 87108; and Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814

C-reactive protein (CRP) is an acute phase reactant with roles in innate host defense, clearance of damaged cells, and regulation of the inflammatory response. These activities of CRP depend on ligand recognition, complement activation, and binding to FcR. CRP binds to phosphocholine in the Streptococcus pneumoniae cell wall and provides innate defense against pneumococcal infection. These studies examine the effect of this early innate defense molecule on the development of Abs and protective immunity to S. pneumoniae. Dendritic cells (DC) initiate and direct the adaptive immune response by integrating innate stimuli with cytokine synthesis and Ag presentation. We hypothesized that CRP would direct uptake of S. pneumoniae to FcR on DC and enhance Ag presentation. CRP opsonization of the R36a strain of S. pneumoniae increased the uptake of bacteria by DC. DC pulsed with untreated or CRP-opsonized R36a were transferred into recipient mice, and Ab responses were measured. In mice challenged with free R36a, CRP opsonization resulted in higher secondary and memory IgG responses to both phosphocholine and pneumococcal surface protein A. Furthermore, mice immunized with DC that had been pulsed with CRP-opsonized R36a showed increased resistance to intranasal infection with virulent S. pneumoniae. The effects of CRP on Ag uptake, Ab responses, and protection from infection all required FcR -chain expression on DC. The results indicate that innate recognition by CRP enhances effective uptake and presentation of bacterial Ags through FcR on DC and stimulates protective adaptive immunity.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Department of Veterans Affairs, National Institutes of Health Grant AI-28358, and the University of New Mexico Initiative for Minority Student Development Program.

² Address correspondence and reprint requests to Dr. Carolyn Mold, Department of Molecular Genetics and Microbiology, MSC08 4660, 1 University of New Mexico, Albuquerque, NM 87131. E-mail address: cmold{at}salud.unm.edu

³ Abbreviations used in this paper: CRP, C-reactive protein; DC, dendritic cell; BMDC, bone marrow-derived DC; PC, phosphocholine; Pn3, S. pneumoniae serotype 3; PspA, pneumococcal surface protein A; CM-DiI, chloromethylbenzamido derivative of 3,3'-dioctadecylindocarbocyanine; PC-BSA, PC conjugated BSA.

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