Role of complement receptors 1 and 2 (CD35 and CD21), C3, C4, and C5 in survival by mice of Staphylococcus aureus bacteremia.
Complement-mediated opsonization and phagocytosis of encapsulated serotype 5 Staphylococcus aureus are essential to host defense. We describe the effects of complement depletion and deficiencies of C4, C5, and complement receptors 1 and 2 on mouse survival after intravenous exposure to S aureus. Depletion of complement proteins in C57BL/6 mice with the use of cobra-venom factor decreased survival compared with that of controls after the induction of bacteremia with mucoid (90% mortality), encapsulated (73%), and unencapsulated (59%) S aureus strains. In this model complement is even more important in the control of infection with encapsulated S aureus (80% of clinical isolates) than in the control of infection by unencapsulated strains. C4-deficient mice demonstrated similar mortality from bacteremia caused by encapsulated S aureus compared with controls, suggesting that in the unimmunized animal the alternative complement pathway contributes more to control of bacteremia caused by encapsulated S aureus than the classical complement pathway or mannan-binding lectin pathway. C5-deficient mice (B10.D2-H2(d) H2-T18(c) Hc(0)/oSnJ) showed similar mortality when subjected to bacteremia caused by encapsulated S aureus compared with C5-sufficient (B10.D2-Hc(1) H2(d) H2-T18(c)/nSnJ) mice, suggesting that in this model the anaphylatoxin C5a and the late complement cascade are not critical to survival of bacteremia induced with the use of these strains. However, C5-deficient mice depleted of C3 with the use of cobra-venom factor had 60% decreased survival compared with untreated C5-deficient mice with bacteremia induced by encapsulated S aureus, suggesting that in this model C3 is more critical than C5 in controlling S aureus bacteremia. Complement receptor 1 (CD35) is the primary receptor for the opsonin C3b. Mice deficient in CD35/CD21 showed a 67% decrease in survival compared with normal mice, suggesting that CD35/CD21 is of major importance in the control of S aureus-induced bacteremia.
Cunnion
Kenji M
KM
Department of Pediatrics and Duke Clinical Research Institue, Duke University Medical Center, Durham, NC, USA. cunniok@chkd.org
Benjamin
Daniel K
DK
Hester
C Garren
CG
Frank
Michael M
MM
D000818:Animals; D016470:Bacteremia / Q000276:immunology*; D003176:Complement C3 / Q000172:deficiency / Q000378:metabolism; D003181:Complement C4 / Q000172:deficiency / Q000378:metabolism; D003182:Complement C5 / Q000172:deficiency / Q000378:metabolism; D003165:Complement System Proteins / Q000172:deficiency / Q000378:metabolism*; D005260:Female; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011951:Receptors, Complement / Q000172:deficiency / Q000378:metabolism*; D017463:Receptors, Complement 3b / Q000172:deficiency / Q000378:metabolism; D017464:Receptors, Complement 3d / Q000172:deficiency / Q000378:metabolism; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology / Q000472:pathogenicity
D003176:Complement C3; D003181:Complement C4; D003182:Complement C5; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D003165:Complement System Proteins