1. Group B streptococcal capsular sialic acids interact with siglecs (immunoglobulin-like lectins) on human leukocytes.
- Author
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Carlin AF, Lewis AL, Varki A, and Nizet V
- Subjects
- Animals, Antigens, CD chemistry, Antigens, Differentiation, Myelomonocytic chemistry, Antigens, Differentiation, Myelomonocytic metabolism, Bacterial Capsules chemistry, CHO Cells, Cricetinae, Cricetulus, Gene Expression Regulation, Humans, Lectins chemistry, Sialic Acids chemistry, Transcriptional Activation, Antigens, CD metabolism, Bacterial Capsules metabolism, Lectins metabolism, Leukocytes metabolism, Sialic Acids metabolism, Streptococcus agalactiae metabolism
- Abstract
Group B Streptococcus (GBS) is classified into nine serotypes that vary in capsular polysaccharide (CPS) architecture but share in common the presence of a terminal sialic acid (Sia) residue. This position and linkage of GBS Sia closely resembles that of cell surface glycans found abundantly on human cells. CD33-related Siglecs (CD33rSiglecs) are a family of Sia-binding lectins expressed on host leukocytes that engage host Sia-capped glycans and send signals that dampen inflammatory gene activation. We hypothesized that GBS evolved to display CPS Sia as a form of molecular mimicry limiting the activation of an effective innate immune response. In this study, we applied a panel of immunologic and cell-based assays to demonstrate that GBS of several serotypes interacts in a Sia- and serotype-specific manner with certain human CD33rSiglecs, including hSiglec-9 and hSiglec-5 expressed on neutrophils and monocytes. Modification of GBS CPS Sia by O acetylation has recently been recognized, and we further show that the degree of O acetylation can markedly affect the interaction between GBS and hSiglec-5, -7, and -9. Thus, production of Sia-capped bacterial polysaccharide capsules that mimic human cell surface glycans in order to engage CD33rSiglecs may be an example of a previously unrecognized bacterial mechanism of leukocyte manipulation.
- Published
- 2007
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