Group B Streptococcus engages an inhibitory Siglec through sialic acid mimicry to blunt innate immune and inflammatory responses in vivo.

Abstract

Group B Streptococcus (GBS) is a common agent of bacterial sepsis and meningitis in newborns. The GBS surface capsule contains sialic acids (Sia) that engage Sia-binding immunoglobulin-like lectins (Siglecs) on leukocytes. Here we use mice lacking Siglec-E, an inhibitory Siglec of myelomonocytic cells, to study the significance of GBS Siglec engagement during in vivo infection. We found GBS bound to Siglec-E in a Sia-specific fashion to blunt NF-κB and MAPK activation. As a consequence, Siglec-E-deficient macrophages had enhanced pro-inflammatory cytokine secretion, phagocytosis and bactericidal activity against the pathogen. Following pulmonary or low-dose intravenous GBS challenge, Siglec-E KO mice produced more pro-inflammatory cytokines and exhibited reduced GBS invasion of the central nervous system. In contrast, upon high dose lethal challenges, cytokine storm in Siglec-E KO mice was associated with accelerated mortality. We conclude that GBS Sia mimicry influences host innate immune and inflammatory responses in vivo through engagement of an inhibitory Siglec, with the ultimate outcome of the host response varying depending upon the site, stage and magnitude of infection.

• Authors: Yung-Chi Chang, Joshua Olson, Federico C Beasley, Christine Tung, Jiquan Zhang, Paul R Crocker, Ajit Varki, Victor Nizet
• Journal: PLoS pathogens (PLoS Pathog) Vol. 10 Issue 1 Pg. e1003846 (Jan 2014) ISSN: 1553-7374 [Electronic] United States
• PMID: 24391502 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Antigens, Differentiation, B-Lymphocyte
• Cytokines
• Siglece protein, mouse
• N-Acetylneuraminic Acid

Topics

• Animals
• Antigens, CD (genetics, immunology)
• Antigens, Differentiation, B-Lymphocyte (genetics, immunology)
• Cytokines (genetics, immunology)
• Humans
• Inflammation (genetics, immunology, pathology)
• Macrophages (immunology, pathology)
• Mice
• Mice, Knockout
• Molecular Mimicry (immunology)
• N-Acetylneuraminic Acid (genetics, immunology)
• Pneumonia, Bacterial (genetics, immunology, pathology)
• Streptococcal Infections (genetics, immunology, pathology)
• Streptococcus agalactiae (immunology)