{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:12:15Z","timestamp":1791231135530,"version":"4.1.0"},"reference-count":42,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,6,2]]},"abstract":"<jats:p>Group B Streptococcus (GBS) causes invasive infections in human newborns. We recently showed that the GBS \u03b2-protein attenuates innate immune responses by binding to sialic acid\u2013binding immunoglobulin-like lectin 5 (Siglec-5), an inhibitory receptor on phagocytes. Interestingly, neutrophils and monocytes also express Siglec-14, which has a ligand-binding domain almost identical to Siglec-5 but signals via an activating motif, raising the possibility that these are paired Siglec receptors that balance immune responses to pathogens. Here we show that \u03b2-protein\u2013expressing GBS binds to both Siglec-5 and Siglec-14 on neutrophils and that the latter engagement counteracts pathogen-induced host immune suppression by activating p38 mitogen-activated protein kinase (MAPK) and AKT signaling pathways. Siglec-14 is absent from some humans because of a SIGLEC14-null polymorphism, and homozygous SIGLEC14-null neutrophils are more susceptible to GBS immune subversion. Finally, we report an unexpected human-specific expression of Siglec-5 and Siglec-14 on amniotic epithelium, the site of initial contact of invading GBS with the fetus. GBS amnion immune activation was likewise influenced by the SIGLEC14-null polymorphism. We provide initial evidence that the polymorphism could influence the risk of prematurity among human fetuses of mothers colonized with GBS. This first functionally proven example of a paired receptor system in the Siglec family has multiple implications for regulation of host immunity.<\/jats:p>","DOI":"10.1084\/jem.20131853","type":"journal-article","created":{"date-parts":[[2014,5,6]],"date-time":"2014-05-06T05:38:37Z","timestamp":1399354717000},"page":"1231-1242","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":200,"title":["Siglec-5 and Siglec-14 are polymorphic paired receptors that modulate neutrophil and amnion signaling responses to group B <i>Streptococcus<\/i>"],"prefix":"10.1084","volume":"211","author":[{"given":"Syed Raza","family":"Ali","sequence":"first","affiliation":[{"name":"Glycobiology Research and Training Center 1 , 2 , 3 , 4 , 5 , and 6"},{"name":"Department of Cellular and Molecular Medicine 1 , 2 , 3 , 4 , 5 , and 6"},{"name":"Department of Pediatrics 1 , 2 , 3 , 4 , 5 , and 6"},{"name":"Department of Pathology 1 , 2 , 3 , 4 , 5 , and 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