Role of macrophage sialoadhesin in host defense against the sialylated pathogen group B Streptococcus.
Several bacterial pathogens decorate their surfaces with sialic acid (Sia) residues within cell wall components or capsular exopolysaccharides. Sialic acid expression can promote bacterial virulence by blocking complement activation or by engagement of inhibitory sialic acid-binding immunoglobulin-like lectins (Siglecs) on host leukocytes. Expressed at high levels on splenic and lymph node macrophages, sialoadhesin (Sn) is a unique Siglec with an elongated structure that lacks intracellular signaling motifs. Sialoadhesin allows macrophage to engage certain sialylated pathogens and stimulate inflammatory responses, but the in vivo significance of sialoadhesin in infection has not been shown. We demonstrate that macrophages phagocytose the sialylated pathogen group B Streptococcus (GBS) and increase bactericidal activity via sialoadhesin-sialic-acid-mediated recognition. Sialoadhesin expression on marginal zone metallophilic macrophages in the spleen trapped circulating GBS and restricted the spread of the GBS to distant organs, reducing mortality. Specific IgM antibody responses to GBS challenge were also impaired in sialoadhesin-deficient mice. Thus, sialoadhesin represents a key bridge to orchestrate innate and adaptive immune defenses against invasive sialylated bacterial pathogens.


CONCLUSIONS
Sialoadhesin is critical for macrophages to phagocytose and clear GBS. Increased GBS organ dissemination in the sialoadhesin-deficient mice. Reduced anti-GBS IgM production in the sialoadhesin-deficient mice.
Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA, 92093, USA.
Yung-Chi
YC
Chang
Joshua
J
Olson
Aaron
A
Louie
Paul R
PR
Crocker
Ajit
A
Varki
Victor
V
Nizet
D000818:Animals; D002478:Cells, Cultured; D017353:Gene Deletion; D054884:Host-Pathogen Interactions; D007075:Immunoglobulin M / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D010587:Phagocytosis; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000235:genetics / Q000276:immunology*; D013290:Streptococcal Infections / Q000276:immunology*; D013292:Streptococcus agalactiae / Q000276:immunology / Q000502:physiology*
D007075:Immunoglobulin M; D063267:Sialic Acid Binding Ig-like Lectin 1