title: The role of myeloid receptors on murine plasmacytoid dendritic cells in induction of type I interferon.
abstract: This study tested the hypothesis that a set of predominantly myeloid restricted receptors (F4/80, CD36, Dectin-1, CD200 receptor and mannan binding lectins) and the broadly expressed CD200 played a role in a key function of plasmacytoid DC (pDC), virally induced type I interferon (IFN) production. The Dectin-1 ligands zymosan, glucan phosphate and the anti-Dectin-1 monoclonal antibody (mAb) 2A11 had no effect on influenza virus induced IFNα/β production by murine splenic pDC. However, mannan, a broad blocking reagent against mannose specific receptors, inhibited IFNα/β production by pDC in response to inactivated influenza virus. Moreover, viral glycoproteins (influenza virus haemagglutinin and HIV-1 gp120) stimulated IFNα/β production by splenocytes in a mannan-inhibitable manner, implicating the function of a lectin in glycoprotein induced IFN production. Lastly, the effect of CD200 on IFN induction was investigated. CD200 knock-out macrophages produced more IFNα than wild-type macrophages in response to polyI:C, a MyD88-independent stimulus, consistent with CD200's known inhibitory effect on myeloid cells. In contrast, blocking CD200 with an anti-CD200 mAb resulted in reduced IFNα production by pDC-containing splenocytes in response to CpG and influenza virus (MyD88-dependent stimuli). This suggests there could be a differential effect of CD200 on MyD88 dependent and independent IFN induction pathways in pDC and macrophages. This study supports the hypothesis that a mannan-inhibitable lectin and CD200 are involved in virally induced type I IFN induction.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX13RE, UK.
authors.forename: Rosalind E
authors.initials: RE
authors.lastname: Seeds
authors.forename: Subhankar
authors.initials: S
authors.lastname: Mukhopadhyay
authors.forename: Ian M
authors.initials: IM
authors.lastname: Jones
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Miller
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D007370:Interferon Type I / Q000378:metabolism; D008351:Mannans / Q000494:pharmacology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009975:Orthomyxoviridae / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D015703:Antigens, CD; D000956:Antigens, Viral; D007370:Interferon Type I; D008351:Mannans; D053594:Myeloid Differentiation Factor 88; C042739:antigens, CD200