Siglec-5 and Siglec-14 are polymorphic paired receptors that modulate neutrophil and amnion signaling responses to group B Streptococcus

Abstract

Siglec-5 and Siglec-14 are shown to be paired inhibitory/activating receptors expressed on neutrophils and amniotic epithelium and modulating immune responses to group B Streptococcus.

Siglec-mediated regulation of immune cell function in disease

“…Siglecs contribute to this process by helping to regulate both innate and adaptive immune responses via interactions with ‘self’ glycans. However, some human pathogens such as group B Streptococcus (GBS) display sialic acid-based ‘non-self’ ligands that can be recognized by ITIM-bearing inhibitory Siglecs, leading to subversion of host immune responses 5, 30, 31 . In addition, some pathogens such as Streptococcus pneumoniae secrete enzymes such as sialidases that can destroy Siglec ligands and promote pathogenicity 32, 33 (Fig.…”

“…The ITIM-containing Siglecs-5 and Siglec-11 are paired with the DAP12-coupled Siglecs-14 and Siglec-16, respectively 3 . The evolution of these activating receptors from their corresponding inhibitory receptors is thought to have been driven by pathogen exploitation of the inhibitory Siglecs, thereby providing the host with additional activitory pathways by which to combat these pathogens 5–8 .…”

Discovery and characterization ofde novosialic acid biosynthesis in the phylumFusobacterium

“…In these bacterial contexts, sialic acids have been shown to shield pathogens from host immune responses by interacting with host sialic acid-binding proteins Chang et al 2014;Inzana et al 2012;Ram et al 1998). For example, roles of bacterial sialic acid mimicry in complement evasion (Factor H) and suppression of neutrophil function (Siglecs) have been described for many different pathogens (Edwards et al 1980(Edwards et al , 1982Pluschke et al 1983;Marques et al 1992;Edwards et al 1993;Gill et al 1996;Kahler et al 1998;Figueira et al 2007Figueira et al , 2008Carlin et al 2009;Ali et al 2014;Chang et al 2014;Inzana et al 2012;Kline et al 2011;Lewis et al 2015;Platt et al 1994;Ram et al 1998;Takahashi et al 1999). Two striking examples of bacterial sialic acid mimicry are the perinatal pathogens Group B Streptococcus (GBS) and Escherichia coli K1.…”

Lectin Galactoside-binding Soluble 3 Binding Protein (LGALS3BP) Is a Tumor-associated Immunomodulatory Ligand for CD33-related Siglecs

“…However, recent experiments described a Siglec-9 high , CD56 dim population of NK cells that were higher in frequency in cancer patients (16) . LGALS3BP could, therefore, also modulate the antitumor NK cell response, as shown for artificial ligands in vitro (39). Because the activating Siglec-14 is a paired receptor with Siglec-5 that emerged because of pathogen-host interactions (13), the first two domains used in Siglec-Fc chimeras for our binding assays differ in only one amino acid and bind to the same set of sialic acid-dependent ligands (13). Therefore, LGALS3BP can be considered to bind activating Siglec-14 in a similar manner as it binds to Siglec-5.…”

“…Although Siglec-1, Siglec-2, Siglec-4, and Siglec-15 have homologs across species, the CD33-related (CD33r) Siglecs (including Siglec-3 (CD33), Siglec-5 through Siglec-14, and Siglec-16 and Siglec-17 in primates) underwent rapid evolutionary changes, and the CD33rSiglec gene cluster (on chromosome 19q in humans) shows high variability between species (6, 10 -12). Primate CD33rSiglecs can be further divided into inhibitory Siglecs, such as Siglec-5, Siglec-7, Siglec-9, and Siglec-10, that transmit inhibitory signals via intracellular immunoreceptor tyrosinebased inhibitory motifs; or, intracellular immunoreceptor tyrosine-based inhibitory motif-like motifs and activating Siglecs, including Siglec-14 and Siglec-16, that activate cells via DAP12 recruitment (6,8,10,11,13).…”