The protective function of human C-reactive protein in mouse models of Streptococcus pneumoniae infection.
Human C-reactive protein (CRP), injected intravenously into mice or produced inside mice by a human transgene, protects mice from death following administration of lethal numbers of Streptococcus pneumoniae. The protective effect of CRP is due to reduction in the concentration of bacteria in the blood. The exact mechanism of CRP-dependent killing of pneumococci and the partners of CRP in this process are yet to be defined. The current efforts to determine the mechanism of action of CRP in mice are directed by four known in vitro functions of CRP: 1. the ability of pneumococcal C-polysaccharide-complexed CRP to activate complement pathways, 2. the ability of CRP to bind to Fcgamma receptors on phagocytic cells, 3. the ability of CRP to bind to immobilized complement regulator protein factor H which can also be present on pneumococci, and, 4. the ability of CRP to interact with dendritic cells. CRP-treated dendritic cells may well be as host-defensive as CRP alone. An interesting condition for the protective function of CRP is that CRP must be given to mice within a few hours of the administration of pneumococci. CRP does not protect mice if given later, suggesting that CRP works prophylactically but not as a treatment for infection. However, full knowledge of CRP may lead to the development of CRP-based treatment strategies to control pneumococcal infection. Also, because CRP deficiency in humans has not yet been reported, it becomes important to investigate the deficiency of the mechanism of action of CRP in CRP-positive individuals.
Agrawal
Alok
A
Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA. agrawal@etsu.edu
Suresh
Madathilparambil V
MV
Singh
Sanjay K
SK
Ferguson
Donald A
DA
D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism / Q000627:therapeutic use*; D017242:Complement Factor H / Q000378:metabolism; D003165:Complement System Proteins / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology; D006801:Humans; D051379:Mice; D011008:Pneumococcal Infections / Q000382:microbiology / Q000517:prevention & control*; D017452:Receptors, IgG / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000378:metabolism
D017452:Receptors, IgG; D017242:Complement Factor H; D003165:Complement System Proteins; D002097:C-Reactive Protein