Group B streptococcal capsular sialic acids interact with siglecs (immunoglobulin-like lectins) on human leukocytes.
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.
Carlin
Aaron F
AF
Department of Pediatrics, Division of Pharmacology and Drug Discovery, University of California, San Diego School of Medicine, Cellular and Molecular Medicine East, La Jolla, CA 92093-0687, USA.
Lewis
Amanda L
AL
Varki
Ajit
A
Nizet
Victor
V
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000737:chemistry / Q000378:metabolism; D016667:Bacterial Capsules / Q000737:chemistry / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005786:Gene Expression Regulation; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D012794:Sialic Acids / Q000737:chemistry / Q000378:metabolism*; D013292:Streptococcus agalactiae / Q000378:metabolism*; D015533:Transcriptional Activation
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D037102:Lectins; D012794:Sialic Acids