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Siglec-5 and Siglec...
Siglec-5 and Siglec-14 are polymorphic paired receptors that modulate neutrophil and amnion signaling responses to group B Streptococcus
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Ali, Syed Raza (författare)
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Fong, Jerry J. (författare)
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Carlin, Aaron F. (författare)
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Busch, Tamara D. (författare)
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Linden, Rebecka (författare)
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Angata, Takashi (författare)
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- Areschoug, Thomas (författare)
- Lund University,Lunds universitet,Avdelningen för medicinsk mikrobiologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Medical Microbiology,Department of Laboratory Medicine,Faculty of Medicine
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Parast, Mana (författare)
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Varki, Nissi (författare)
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Murray, Jeffrey (författare)
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Nizet, Victor (författare)
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Varki, Ajit (författare)
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(creator_code:org_t)
- 2014-05-05
- 2014
- Engelska.
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 211:6, s. 1231-1242
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
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Ali, Syed Raza
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Fong, Jerry J.
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Carlin, Aaron F.
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Busch, Tamara D.
-
Linden, Rebecka
-
Angata, Takashi
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visa fler...
-
Areschoug, Thoma ...
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Parast, Mana
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Varki, Nissi
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Murray, Jeffrey
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Nizet, Victor
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Varki, Ajit
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visa färre...
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