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Blood, 2 April 2009, Vol. 113, No. 14, pp. 3333-3336. Prepublished online as a Blood First Edition Paper on February 4, 2009; DOI 10.1182/blood-2008-11-187302. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-11-187302v1 113/14/3333    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Carlin, A. F. Articles by Varki, A. Search for Related Content PubMed PubMed Citation Articles by Carlin, A. F. Articles by Varki, A. Related Collections Phagocytes, Granulocytes, and Myelopoiesis Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS Brief report Molecular mimicry of host sialylated glycans allows a bacterial pathogen to engage neutrophil Siglec-9 and dampen the innate immune response Aaron F. Carlin1,*, Satoshi Uchiyama1,*, Yung-Chi Chang1, Amanda L. Lewis1, Victor Nizet1, and Ajit Varki1 1 Departments of Medicine, Pediatrics, and Cellular & Molecular Medicine, University of California, San Diego, La Jolla Human neutrophil Siglec-9 is a lectin that recognizes sialic acids (Sias) via an amino-terminal V-set Ig domain and possesses tyrosine-based inhibitory motifs in its cytoplasmic tail. We hypothesized that Siglec-9 recognizes host Sias as "self," including in cis interactions with Sias on the neutrophil's own surface, thereby dampening unwanted neutrophil reactivity. Here we show that neutrophils presented with immobilized multimerized Sia2-3Galβ1-4GlcNAc units engage them in trans via Siglec-9. The sialylated capsular polysaccharide of group B Streptococcus (GBS) also presents terminal Sia2-3Galβ1-4GlcNAc units, and similarly engages neutrophil Siglec-9, dampening neutrophil responses in a Sia- and Siglec-9–dependent manner. Reduction in the neutrophil oxidative burst, diminished formation of neutrophil extracellular DNA traps, and increased bacterial survival are also facilitated by GBS sialylated capsular polysaccharide interactions with Siglec-9. Thus, GBS can impair neutrophil defense functions by coopting a host inhibitory receptor via sialoglycan molecular mimicry, a novel mechanism of bacterial immune evasion. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Weiman, S. Dahesh, A. F Carlin, A. Varki, V. Nizet, and A. L Lewis Genetic and biochemical modulation of sialic acid O-acetylation on group B Streptococcus: Phenotypic and functional impact Glycobiology, November 1, 2009; 19(11): 1204 - 1213. [Abstract] [Full Text] [PDF] A. L. Lewis, N. Desa, E. E. Hansen, Y. A. Knirel, J. I. Gordon, P. Gagneux, V. Nizet, and A. Varki Innovations in host and microbial sialic acid biosynthesis revealed by phylogenomic prediction of nonulosonic acid structure PNAS, August 11, 2009; 106(32): 13552 - 13557. [Abstract] [Full Text] [PDF] A. F. Carlin, Y.-C. Chang, T. Areschoug, G. Lindahl, N. Hurtado-Ziola, C. C. King, A. Varki, and V. Nizet Group B Streptococcus suppression of phagocyte functions by protein-mediated engagement of human Siglec-5 J. Exp. Med., August 3, 2009; 206(8): 1691 - 1699. [Abstract] [Full Text] [PDF] A. Varki Natural ligands for CD33-related Siglecs? Glycobiology, August 1, 2009; 19(8): 810 - 812. [Full Text] [PDF]

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