Rapid evolution of binding specificities and expression patterns of inhibitory CD33-related Siglecs in primates

Vered Padler-Karavani, Nancy Hurtado-Ziola, Yung Chi Chang, Justin L. Sonnenburg, Arash Ronaghy, Hai Yu, Andrea Verhagen, Victor Nizet, Xi Chen, Nissi Varki, Ajit Varki, Takashi Angata

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Siglecs are sialic acid-binding Ig-like lectins that recognize sialoglycans via amino-terminal V-set domains. CD33-related Siglecs (CD33rSiglecs) on innate immune cells recognize endogenous sialoglycans as "self-associated molecular patterns" (SAMPs), dampening immune responses via cytosolic immunoreceptor tyrosine- based inhibition motifs that recruit tyrosine phosphatases. However, sialic acid-expressing pathogens subvert this mechanism through molecular mimicry. Meanwhile, endogenous host SAMPs must continually evolve to evade other pathogens that exploit sialic acids as invasion targets. We hypothesized that these opposing selection forces have accelerated CD33rSiglec evolution. We address this by comparative analysis of major CD33rSiglec (Siglec-3, Siglec-5, and Siglec-9) orthologs in humans, chimpanzees, and baboons. Recombinant soluble molecules displaying ligand- binding domains show marked quantitative and qualitative interspecies differences in interactions with strains of the sialylated pathogen, group B Streptococcus, and with sialoglycans presented as gangliosides or in the form of sialoglycan microarrays, including variations such as N-glycolyl and O-acetyl groups. Primate Siglecs also show quantitative and qualitative intra- and interspecies variations in expression patterns on leukocytes, both in circulation and in tissues. Taken together our data explain why the CD33rSiglec-encoding gene cluster is undergoing rapid evolution via multiple mechanisms, driven by the need to maintain selfrecognition by innate immune cells, while escaping 2 distinct mechanisms of pathogen subversion.

Original languageEnglish (US)
Pages (from-to)1280-1293
Number of pages14
JournalFASEB Journal
Volume28
Issue number3
DOIs
StatePublished - 2014

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Sialic Acid Binding Immunoglobulin-like Lectins
Primates
Pathogens
Immunoreceptor Tyrosine-Based Inhibition Motif
Tyrosine
Sialic Acid Binding Ig-like Lectin 3
Molecular Mimicry
Sialic Acids
Gene encoding
Streptococcus agalactiae
Pan troglodytes
Papio
Gangliosides
N-Acetylneuraminic Acid
Microarrays
Multigene Family
Phosphoric Monoester Hydrolases
Leukocytes
Tissue
Ligands

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology
  • Medicine(all)

Cite this

Padler-Karavani, V., Hurtado-Ziola, N., Chang, Y. C., Sonnenburg, J. L., Ronaghy, A., Yu, H., ... Angata, T. (2014). Rapid evolution of binding specificities and expression patterns of inhibitory CD33-related Siglecs in primates. FASEB Journal, 28(3), 1280-1293. https://doi.org/10.1096/fj.13-241497

Rapid evolution of binding specificities and expression patterns of inhibitory CD33-related Siglecs in primates. / Padler-Karavani, Vered; Hurtado-Ziola, Nancy; Chang, Yung Chi; Sonnenburg, Justin L.; Ronaghy, Arash; Yu, Hai; Verhagen, Andrea; Nizet, Victor; Chen, Xi; Varki, Nissi; Varki, Ajit; Angata, Takashi.

In: FASEB Journal, Vol. 28, No. 3, 2014, p. 1280-1293.

Research output: Contribution to journalArticle

Padler-Karavani, V, Hurtado-Ziola, N, Chang, YC, Sonnenburg, JL, Ronaghy, A, Yu, H, Verhagen, A, Nizet, V, Chen, X, Varki, N, Varki, A & Angata, T 2014, 'Rapid evolution of binding specificities and expression patterns of inhibitory CD33-related Siglecs in primates', FASEB Journal, vol. 28, no. 3, pp. 1280-1293. https://doi.org/10.1096/fj.13-241497
Padler-Karavani V, Hurtado-Ziola N, Chang YC, Sonnenburg JL, Ronaghy A, Yu H et al. Rapid evolution of binding specificities and expression patterns of inhibitory CD33-related Siglecs in primates. FASEB Journal. 2014;28(3):1280-1293. https://doi.org/10.1096/fj.13-241497
Padler-Karavani, Vered ; Hurtado-Ziola, Nancy ; Chang, Yung Chi ; Sonnenburg, Justin L. ; Ronaghy, Arash ; Yu, Hai ; Verhagen, Andrea ; Nizet, Victor ; Chen, Xi ; Varki, Nissi ; Varki, Ajit ; Angata, Takashi. / Rapid evolution of binding specificities and expression patterns of inhibitory CD33-related Siglecs in primates. In: FASEB Journal. 2014 ; Vol. 28, No. 3. pp. 1280-1293.
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