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Infection and Immunity, December 2005, p. 8188-8193, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8188-8193.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Relative Roles of Complement Factor 3 and Mannose-Binding Lectin in Host Defense against Infection

Kazue Takahashi,^* Lei Shi,^, Lakshmi D. Gowda, and R. Alan B. Ezekowitz

Laboratory of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Received 14 June 2005/ Returned for modification 18 August 2005/ Accepted 6 September 2005

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.

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* Corresponding author. Mailing address: Laboratory of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, GRJ 1402, Boston, MA 02114. Phone: (617) 726-1394. Fax: (617) 724-3248. E-mail: ktakahashi1{at}partners.org.

Editor: J. B. Bliska

Co-first authors.

Present address: Centocor Inc., Mail Code R32, 145 King of Prussia Rd., Radnor, PA 19087.

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Infection and Immunity, December 2005, p. 8188-8193, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8188-8193.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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