Dendritic cell-derived exosomes express a Streptococcus pneumoniae capsular polysaccharide type 14 cross-reactive antigen that induces protective immunoglobulin responses against pneumococcal infection in mice.
Exosomes activate T cells in vivo, but whether exosomes are able to induce humoral immune responses is still unknown. We found that dendritic cells, but not other immune cells, constitutively release an exosome-associated glycoconjugate that is cross-reactive with the capsular polysaccharide of Streptococcus pneumoniae type 14 (Cps14-CRA). Cps14-CRA was localized to the cholesterol-enriched microdomains or rafts of the exosomes and was mapped to the beta1-->6 branched N-acetyl-lactosamine derivatives of the Cps14-CRA. Injection of CFA-primed naive mice with purified dendritic cell exosomes induced immunoglobulin (Ig) anti-Cps14 responses composed predominantly of IgM, IgG3, and IgG1. These responses were associated with protection against a lethal challenge with live S. pneumoniae type 14, but not with type 3 bacteria, and was correlated with the titer of elicited IgM and IgG3 anti-Cps14. These data show, for the first time, that exosomes can induce a humoral immune response to an associated unprocessed, autologous antigen. Although anti-Cps14 Ig responses are specifically demonstrated, these could reflect a broader mechanism that modulates both natural immunity and autoimmunity to other glycotopes.
Colino
Jesus
J
Department of Pathology, Uniformed Services University of the Health Sciences (USUHS), 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
Snapper
Clifford M
CM
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D016667:Bacterial Capsules / Q000276:immunology*; D003429:Cross Reactions; D022162:Cytoplasmic Vesicles / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D021962:Membrane Microdomains / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011008:Pneumococcal Infections / Q000276:immunology* / Q000517:prevention & control; D011134:Polysaccharides / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology
D000942:Antigens, Bacterial; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011134:Polysaccharides