SIGN-R1 contributes to protection against lethal pneumococcal infection in mice.
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.
Lanoue
Astrid
A
Laboratory of Molecular Biology, Medical Research Council, Hills Rd., Cambridge CB2 2QH, England, UK.
Clatworthy
Menna R
MR
Smith
Philippa
P
Green
Sheila
S
Townsend
Michael J
MJ
Jolin
Helen E
HE
Smith
Kenneth G C
KG
Fallon
Padraic G
PG
McKenzie
Andrew N J
AN
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D015815:Cell Adhesion Molecules; D003001:Cloning, Molecular; D003911:Dextrans / Q000378:metabolism; D005260:Female; D007113:Immunity, Innate; D037181:Lectins, C-Type / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D011008:Pneumococcal Infections / Q000276:immunology*; D011956:Receptors, Cell Surface; D013296:Streptococcus pneumoniae / Q000276:immunology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000907:Antibodies, Bacterial; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D003911:Dextrans; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin