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C-Reactive Protein Increases Cytokine Responses to Streptococcus pneumoniae through Interactions with Fc Receptors¹

Carolyn Mold^2, and Terry W. Du Clos^*,

^* Veterans Affairs Medical Center, Albuquerque, NM 87108; and Departments of Internal Medicine and Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131

Streptococcus pneumoniae is the most common organism responsible for community acquired pneumonia and meningitis. In pneumococcal pneumonia, a strong local inflammatory cytokine response reduces the frequency of bacteremia and increases survival. The initiation of this cytokine response by innate recognition of bacterial cell wall components through TLR has been described, but the role of soluble innate mediators has received limited attention. C-reactive protein (CRP) is an acute phase protein that binds phosphocholine residues on S. pneumoniae cell walls. CRP interacts with phagocytic cells through FcRI and FcRII and activates the classical complement pathway. CRP is protective in mouse pneumococcal bacteremia by increasing complement-dependent clearance and killing of bacteria. We studied the cytokine response of PBMC stimulated with CRP-opsonized S. pneumoniae to determine the effect of CRP interaction with FcR. CRP dramatically increased the production of TNF- and IL-1 in response to S. pneumoniae. These increases were blocked by phosphocholine, which inhibits CRP binding to S. pneumoniae, by inhibitors of FcR signaling, and by mAb to FcRI and FcRII. A mutated rCRP with decreased FcR binding had a decreased ability to stimulate TNF- release, compared with wild-type CRP. Individuals who were homozygous for the R-131 allele of FcRIIA, which has a higher affinity for CRP, showed higher responses to CRP-opsonized bacteria than did individuals homozygous for the H-131 allele, further implicating this receptor. The results indicate that CRP recognition of S. pneumoniae and binding to FcR may enhance the early protective cytokine response to infection.

This article has been cited by other articles:

				D. Thomas-Rudolph, T. W. Du Clos, C. M. Snapper, and C. Mold C-Reactive Protein Enhances Immunity to Streptococcus pneumoniae by Targeting Uptake to Fc{gamma}R on Dendritic Cells J. Immunol., June 1, 2007; 178(11): 7283 - 7291. [Abstract] [Full Text] [PDF]