The Journal of Experimental Medicine
ThymUS '08
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Published 6 December 2004. doi:10.1084/jem.20040795
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 11, 1383-1393
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SIGN-R1 Contributes to Protection against Lethal Pneumococcal Infection in Mice

Astrid Lanoue1, Menna R. Clatworthy2, Philippa Smith1, Sheila Green1, Michael J. Townsend1, Helen E. Jolin1, Kenneth G.C. Smith2, Padraic G. Fallon3, and Andrew N.J. McKenzie1

1 Laboratory of Molecular Biology, Medical Research Council, Cambridge CB2 2QH, England, UK
2 Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge CB2 2XY, England, UK
3 Department of Biochemistry, Trinity College, Dublin 2, Ireland

Address correspondence to Andrew N.J. McKenzie, Laboratory of Molecular Biology, Medical Research Council, Hills Rd., Cambridge CB2 2QH, England, UK. Phone: 44-1223-402350; Fax: 44-1223-412178; email: anm{at}mrc-lmb.cam.ac.uk

Rapid clearance of pathogens is essential for successful control of pyogenic bacterial infection. Previous experiments have shown that antibody to specific intracellular adhesion molecule-grabbing nonintegrin (SIGN)-R1 inhibits uptake of capsular polysaccharide by marginal zone macrophages, suggesting a role for SIGN-R1 in this process. We now demonstrate that mice lacking SIGN-R1 (a mouse homologue of human dendritic cell–SIGN receptor) are significantly more susceptible to Streptococcus pneumoniae infection and fail to clear S. pneumoniae from the circulation. Marginal zone and peritoneal macrophages show impaired bacterial recognition associated with an inability to bind T-independent type 2 antigens such as dextran. Our work represents the first evidence for a protective in vivo role for a SIGN family molecule.

Key Words: DC-SIGN • marginal zone macrophages • microbial infection • innate immunity • lectin

A. Lanoue and M.R. Clatworthy contributed equally to this work.

M.J. Townsend's present address is Dept. of Immunology and Infectious Diseases, Harvard School of Public Health, Rm. 205, 651 Huntingdon Ave., Boston, MA 02115.

Abbreviations used in this paper: aa, amino acids; CRD, carbohydrate recognition domain; MZ, marginal zone; MZM, MZ macrophage; PC, phosphorylcholine; PRR, pattern recognition receptor; SIGN, specific intracellular adhesion molecule-grabbing nonintegrin; TI-2, thymus independent type 2.


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