Relative roles of complement factor 3 and mannose-binding lectin in host defense against infection.
Staphylococcus aureus is a major cause of severe nosocomial and community-acquired infections. Phagocytes and humoral molecules, including complement, have been proposed to cooperate in host defense against gram-positive bacteria. Circumstantial evidence indicates a role for complement, but this has not been formally defined. Complement activation is initiated by the classical, alternative, or lectin pathway, with the latter requiring mannose-binding lectin (MBL, also known as mannose-binding protein). MBL is an oligomeric serum protein that recognizes carbohydrates decorating a broad range of infectious agents, including S. aureus. We previously reported that MBL null mice were highly susceptible to S. aureus infection, confirming that MBL plays a key role in first-line host defense. In this study, we evaluated the relative roles of C3 and MBL against S. aureus infection by generating MBL x C3 null mice to compare with C3 single null mice. C3 deficiency alone significantly reduced survival to 19% from 97% of wild-type mice (P < 0.0001). Surprisingly, an additional MBL deficiency reduced the survival further to 7% (P < 0.0001). However, the MBL deficiency alone had a smaller though significant effect on survival, which was 77% (P = 0.018 versus wild-type mice). These results confirm an essential function for complement in host resistance against S. aureus infection but also identify an MBL-dependent mechanism that is C3 independent.
Takahashi
Kazue
K
Laboratory of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, GRJ 1402, Boston, MA 02114, USA. ktakahashi1@partners.org
Shi
Lei
L
Gowda
Lakshmi D
LD
Ezekowitz
R Alan B
RA
D000818:Animals; D016470:Bacteremia / Q000235:genetics / Q000276:immunology; D003176:Complement C3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D037601:Mannose-Binding Lectin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology*; D013211:Staphylococcus aureus
D003176:Complement C3; D037601:Mannose-Binding Lectin