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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
- Article/chapterEnglish2014
Publisher, publication year, extent ...
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2014-05-05
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Rockefeller University Press,2014
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LIBRIS-ID:oai:lup.lub.lu.se:aaa06cf1-c47c-4673-9ad9-5bfc65e85ba9
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https://lup.lub.lu.se/record/4609589URI
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https://doi.org/10.1084/jem.20131853DOI
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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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.
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Fong, Jerry J.
(author)
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Carlin, Aaron F.
(author)
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Busch, Tamara D.
(author)
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Linden, Rebecka
(author)
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Angata, Takashi
(author)
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Areschoug, ThomasLund University,Lunds universitet,Avdelningen för medicinsk mikrobiologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Medical Microbiology,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)mmb-tar
(author)
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Parast, Mana
(author)
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Varki, Nissi
(author)
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Murray, Jeffrey
(author)
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Nizet, Victor
(author)
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Varki, Ajit
(author)
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Avdelningen för medicinsk mikrobiologiInstitutionen för laboratoriemedicin
(creator_code:org_t)
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In:Journal of Experimental Medicine: Rockefeller University Press211:6, s. 1231-12421540-95380022-1007
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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.
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Linden, Rebecka
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Angata, Takashi
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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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- MEDICAL AND HEALTH SCIENCES
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Lund University