title: The CD169 sialoadhesin molecule mediates cytotoxic T-cell responses to tumour apoptotic vesicles.
abstract: Apoptosis leads to the fragmentation and packaging of cellular contents into discrete vesicles, a process known as 'blebbing'. Extracellular vesicles express membrane-bound sialic acids, which enable their capture by CD169 (sialoadhesin; Siglec-1) expressing macrophages in the lymph node and spleen. Furthermore, CD169 mediates vesicle trafficking and suppresses the immune response to exosomes-a type of extracellular vesicle released from living cells. In this study, we found that CD169(+) macrophages were the predominant splenic macrophage subset responsible for the capture of EL4 lymphoma-derived apoptotic vesicles (ApoVs) from circulation. CD169(-/-) mice had significantly enhanced in vivo cytotoxic T lymphocyte responses to antigen-pulsed ApoVs, indicating a suppressive role for CD169(+) macrophages to ApoV-associated antigen. In contrast to the observed immunogenic role of ApoVs, the co-administration of unpulsed ApoVs with antigen-pulsed dendritic cells (DCs) significantly suppressed DC-mediated cytotoxic response in vivo; however, this occurred independent of CD169 expression. Overall, our results confirm that apoptosis contributes to both tolerance and immunity, as well as establishing CD169 as a critical mediator of the immune response to extracellular vesicles.
authors.affiliation: Department of Microbiology and Immunology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Lane Vc
authors.initials: LV
authors.lastname: Black
authors.affiliation: Department of Microbiology and Immunology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Saunderson
authors.affiliation: Department of Microbiology and Immunology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Frazer P
authors.initials: FP
authors.lastname: Coutinho
authors.affiliation: Department of Microbiology and Immunology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Morad-Rémy
authors.initials: MR
authors.lastname: Muhsin-Sharafaldine
authors.affiliation: Department of Microbiology and Immunology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Tanvi T
authors.initials: TT
authors.lastname: Damani
authors.affiliation: Department of Microbiology and Immunology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Dunn
authors.affiliation: Department of Microbiology and Immunology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: McLellan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019921:Biotinylation; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D000067128:Extracellular Vesicles / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008223:Lymphoma / Q000276:immunology* / Q000473:pathology*; D008810:Mice, Inbred C57BL; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects
chemical_list: D063267:Sialic Acid Binding Ig-like Lectin 1; D004317:Doxorubicin; D019311:Staurosporine