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

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Siglec-5 and Siglec-14 are polymorphic paired receptors that modulate neutrophil and amnion signaling responses to group B Streptococcus. / Ali, Syed Raza; Fong, Jerry J.; Carlin, Aaron F.; Busch, Tamara D.; Linden, Rebecka; Angata, Takashi; Areschoug, Thomas; Parast, Mana; Varki, Nissi; Murray, Jeffrey; Nizet, Victor; Varki, Ajit.

I: Journal of Experimental Medicine, Vol. 211, Nr. 6, 2014, s. 1231-1242.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Ali, SR, Fong, JJ, Carlin, AF, Busch, TD, Linden, R, Angata, T, Areschoug, T, Parast, M, Varki, N, Murray, J, Nizet, V & Varki, A 2014, 'Siglec-5 and Siglec-14 are polymorphic paired receptors that modulate neutrophil and amnion signaling responses to group B Streptococcus', Journal of Experimental Medicine, vol. 211, nr. 6, s. 1231-1242. https://doi.org/10.1084/jem.20131853

APA

CBE

Ali SR, Fong JJ, Carlin AF, Busch TD, Linden R, Angata T, Areschoug T, Parast M, Varki N, Murray J, Nizet V, Varki A. 2014. Siglec-5 and Siglec-14 are polymorphic paired receptors that modulate neutrophil and amnion signaling responses to group B Streptococcus. Journal of Experimental Medicine. 211(6):1231-1242. https://doi.org/10.1084/jem.20131853

MLA

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Author

Ali, Syed Raza ; Fong, Jerry J. ; Carlin, Aaron F. ; Busch, Tamara D. ; Linden, Rebecka ; Angata, Takashi ; Areschoug, Thomas ; Parast, Mana ; Varki, Nissi ; Murray, Jeffrey ; Nizet, Victor ; Varki, Ajit. / Siglec-5 and Siglec-14 are polymorphic paired receptors that modulate neutrophil and amnion signaling responses to group B Streptococcus. I: Journal of Experimental Medicine. 2014 ; Vol. 211, Nr. 6. s. 1231-1242.

RIS

TY - JOUR

T1 - Siglec-5 and Siglec-14 are polymorphic paired receptors that modulate neutrophil and amnion signaling responses to group B Streptococcus

AU - Ali, Syed Raza

AU - Fong, Jerry J.

AU - Carlin, Aaron F.

AU - Busch, Tamara D.

AU - Linden, Rebecka

AU - Angata, Takashi

AU - Areschoug, Thomas

AU - Parast, Mana

AU - Varki, Nissi

AU - Murray, Jeffrey

AU - Nizet, Victor

AU - Varki, Ajit

PY - 2014

Y1 - 2014

N2 - Group B Streptococcus (GBS) causes invasive infections in human newborns. We recently showed that the GBS beta-protein attenuates innate immune responses by binding to sialic acid-binding 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 beta-protein-expressing 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.

AB - Group B Streptococcus (GBS) causes invasive infections in human newborns. We recently showed that the GBS beta-protein attenuates innate immune responses by binding to sialic acid-binding 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 beta-protein-expressing 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.

U2 - 10.1084/jem.20131853

DO - 10.1084/jem.20131853

M3 - Article

VL - 211

SP - 1231

EP - 1242

JO - Journal of Experimental Medicine

T2 - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 1540-9538

IS - 6

ER -