title: Sialoadhesin promotes rapid proinflammatory and type I IFN responses to a sialylated pathogen, Campylobacter jejuni.
abstract: Sialoadhesin (Sn) is a macrophage (Mφ)-restricted receptor that recognizes sialylated ligands on host cells and pathogens. Although Sn is thought to be important in cellular interactions of Mφs with cells of the immune system, the functional consequences of pathogen engagement by Sn are unclear. As a model system, we have investigated the role of Sn in Mφ interactions with heat-killed Campylobacter jejuni expressing a GD1a-like, sialylated glycan. Compared to Sn-expressing bone marrow-derived macrophages (BMDM) from wild-type mice, BMDM from mice either deficient in Sn or expressing a non-glycan-binding form of Sn showed greatly reduced phagocytosis of sialylated C. jejuni. This was accompanied by a strong reduction in MyD88-dependent secretion of TNF-α, IL-6, IL-12, and IL-10. In vivo studies demonstrated that functional Sn was required for rapid TNF-α and IFN-β responses to i.v.-injected sialylated C. jejuni. Bacteria were captured within minutes after i.v. injection and were associated with Mφs in both liver and spleen. In the spleen, IFN-β-reactive cells were localized to Sn⁺ Mφs and other cells in the red pulp and marginal zone. Together, these studies demonstrate that Sn plays a key role in capturing sialylated pathogens and promoting rapid proinflammatory cytokine and type I IFN responses.
authors.affiliation: Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom.
authors.forename: Mariliis
authors.initials: M
authors.lastname: Klaas
authors.forename: Cornelia
authors.initials: C
authors.lastname: Oetke
authors.forename: Leanne E
authors.initials: LE
authors.lastname: Lewis
authors.forename: Lars P
authors.initials: LP
authors.lastname: Erwig
authors.forename: Astrid P
authors.initials: AP
authors.lastname: Heikema
authors.forename: Alistair
authors.initials: A
authors.lastname: Easton
authors.forename: Hugh J
authors.initials: HJ
authors.lastname: Willison
authors.forename: Paul R
authors.initials: PR
authors.lastname: Crocker
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D016123:Campylobacter jejuni / Q000276:immunology* / Q000472:pathogenicity*; D002478:Cells, Cultured; D005260:Female; D055879:Gene Knock-In Techniques; D054884:Host-Pathogen Interactions / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D007370:Interferon Type I / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000378:metabolism* / Q000502:physiology; D063267:Sialic Acid Binding Ig-like Lectin 1; D012795:Sialoglycoproteins / Q000378:metabolism* / Q000502:physiology; D013997:Time Factors
chemical_list: D018836:Inflammation Mediators; D007370:Interferon Type I; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D063267:Sialic Acid Binding Ig-like Lectin 1; D012795:Sialoglycoproteins; C571167:Siglec1 protein, mouse