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.
SIGN-R1 Contributes to Protection against Lethal Pneumococcal Infection in Mice
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.
Astrid Lanoue, Menna R. Clatworthy, Philippa Smith, Sheila Green, Michael J. Townsend, Helen E. Jolin, Kenneth G.C. Smith, Padraic G. Fallon, Andrew N.J. McKenzie; SIGN-R1 Contributes to Protection against Lethal Pneumococcal Infection in Mice . J Exp Med 6 December 2004; 200 (11): 1383–1393. doi: https://doi.org/10.1084/jem.20040795
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