title: Cutting edge: DNA sensing via the STING adaptor in myeloid dendritic cells induces potent tolerogenic responses.
abstract: Cytosolic DNA sensing via the stimulator of IFN genes (STING) adaptor incites autoimmunity by inducing type I IFN (IFN-αβ). In this study, we show that DNA is also sensed via STING to suppress immunity by inducing IDO. STING gene ablation abolished IFN-αβ and IDO induction by dendritic cells (DCs) after DNA nanoparticle (DNP) treatment. Marginal zone macrophages, some DCs, and myeloid cells ingested DNPs, but CD11b(+) DCs were the only cells to express IFN-β, whereas CD11b(+) non-DCs were major IL-1β producers. STING ablation also abolished DNP-induced regulatory responses by DCs and regulatory T cells, and hallmark regulatory responses to apoptotic cells were also abrogated. Moreover, systemic cyclic diguanylate monophosphate treatment to activate STING induced selective IFN-β expression by CD11b(+) DCs and suppressed Th1 responses to immunization. Thus, previously unrecognized functional diversity among physiologic innate immune cells regarding DNA sensing via STING is pivotal in driving immune responses to DNA.
authors.affiliation: Cancer Immunology, Inflammation and Tolerance Program, Cancer Center, Augusta, GA 30912;
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.forename: Lingqian
authors.initials: L
authors.lastname: Li
authors.forename: Henrique
authors.initials: H
authors.lastname: Lemos
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Chandler
authors.forename: Gabriela
authors.initials: G
authors.lastname: Pacholczyk
authors.forename: Babak
authors.initials: B
authors.lastname: Baban
authors.forename: Glen N
authors.initials: GN
authors.lastname: Barber
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayakawa
authors.forename: Tracy L
authors.initials: TL
authors.lastname: McGaha
authors.forename: Buvana
authors.initials: B
authors.lastname: Ravishankar
authors.forename: David H
authors.initials: DH
authors.lastname: Munn
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Mellor
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D016898:Interferon-alpha / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D000099197:STING Protein
chemical_list: D039481:CD11b Antigen; D006152:Cyclic GMP; D004247:DNA; D018984:Epitopes, T-Lymphocyte; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016898:Interferon-alpha; D016899:Interferon-beta; D008565:Membrane Proteins; C530855:Sting1 protein, mouse; D000099197:STING Protein; C062025:bis(3',5')-cyclic diguanylic acid