Neutrophil extracellular traps mediate transfer of cytoplasmic neutrophil antigens to myeloid dendritic cells toward ANCA induction and associated autoimmunity

Blood - Tập 120 Số 15 - Trang 3007-3018 - 2012
Sabina Sangaletti1, Claudio Tripodo2, Claudia Chiodoni1, Carla Guarnotta2, Barbara Cappetti1, Patrizia Casalini3, Silvia Piconese1, Mariella Parenza1, Cristiana Guiducci4, Caterina Vitali1, Mario P. Colombo1
1Molecular Immunology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori, Milan, Italy;
2Department of Human Pathology, University of Palermo, Palermo, Italy
3Molecular Targeting Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori, Milan, Italy; and
4Dynavax Technologies Corporation, Berkeley, CA

Tóm tắt

AbstractAntineutrophil cytoplasmic antibodies (ANCAs) target proteins normally retained within neutrophils, indicating that cell death is involved in the autoimmunity process. Still, ANCA pathogenesis remains obscure. ANCAs activate neutrophils inducing their respiratory burst and a peculiar form of cell death, named NETosis, characterized by formation of neutrophil extracellular traps (NETs), decondensed chromatin threads decorated with cytoplasmic proteins endorsed with antimicrobial activity. NETs have been consistently detected in ANCA-associated small-vessel vasculitis, and this association prompted us to test whether the peculiar structure of NET favors neutrophil proteins uploading into myeloid dendritic cells and the induction of ANCAs and associated autoimmunity. Here we show that myeloid DCs uploaded with and activated by NET components induce ANCA and autoimmunity when injected into naive mice. DC uploading and autoimmunity induction are prevented by NET treatment with DNAse, indicating that NET structural integrity is needed to maintain the antigenicity of cytoplasmic proteins. We found NET intermingling with myeloid dendritic cells also positive for neutrophil myeloperoxidase in myeloperoxidase-ANCA-associated microscopic poliangiitis providing a potential correlative picture in human pathology. These data provide the first demonstration that NET structures are highly immunogenic such to trigger adaptive immune response relevant for autoimmunity.

Từ khóa


Tài liệu tham khảo

Nathan, 2006, Neutrophils and immunity: challenges and opportunities., Nat Rev Immunol, 6, 173, 10.1038/nri1785

Di Carlo, 2001, The intriguing role of polymorphonuclear neutrophils in antitumor reactions., Blood, 97, 339, 10.1182/blood.V97.2.339

Cassatella, 2009, Never underestimate the power of a neutrophil., Immunity, 31, 698, 10.1016/j.immuni.2009.10.003

Brinkmann, 2004, Neutrophil extracellular traps kill bacteria., Science, 303, 1532, 10.1126/science.1092385

Fuchs, 2007, Novel cell death program leads to neutrophil extracellular traps., J Cell Biol, 176, 231, 10.1083/jcb.200606027

Remijsen, 2011, Dying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality., Cell Death Differ, 18, 581, 10.1038/cdd.2011.1

Alcorta, 2007, Leukocyte gene expression signatures in antineutrophil cytoplasmic autoantibody and lupus glomerulonephritis., Kidney Int, 72, 853, 10.1038/sj.ki.5002371

Bennett, 2003, Interferon and granulopoiesis signatures in systemic lupus erythematosus blood., J Exp Med, 197, 711, 10.1084/jem.20021553

Lande, 2011, Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus., Sci Transl Med, 3, 73ra19, 10.1126/scitranslmed.3001180

Garcia-Romo, 2011, Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus., Sci Transl Med, 3, 73ra20, 10.1126/scitranslmed.3001201

Villanueva, 2011, Netting neutrophils induce endothelial damage, infiltrate tissues, and expose immunostimulatory molecules in systemic lupus erythematosus., J Immunol, 187, 538, 10.4049/jimmunol.1100450

Kessenbrock, 2009, Netting neutrophils in autoimmune small-vessel vasculitis., Nat Med, 15, 623, 10.1038/nm.1959

Falk, 1992, Anti-myeloperoxidase autoantibodies react with native but not denatured myeloperoxidase., Clin Exp Immunol, 89, 274, 10.1111/j.1365-2249.1992.tb06944.x

Specks, 2000, What you should know about PR3-ANCA: conformational requirements of proteinase 3 (PR3) for enzymatic activity and recognition by PR3-ANCA., Arthritis Res, 2, 263, 10.1186/ar99

Colombo, 1992, Granulocyte colony-stimulating factor (G-CSF) gene transduction in murine adenocarcinoma drives neutrophil-mediated tumor inhibition in vivo: neutrophils discriminate between G-CSF-producing and G-CSF-nonproducing tumor cells., J Immunol, 149, 113, 10.4049/jimmunol.149.1.113

Ziegler-Heitbrock, 2010, Nomenclature of monocytes and dendritic cells in blood., Blood, 116, e74, 10.1182/blood-2010-02-258558

Sangaletti, 2005, Accelerated dendritic-cell migration and T-cell priming in SPARC-deficient mice., J Cell Sci, 118, 3685, 10.1242/jcs.02474

Wernick, 1993, Reliability of histologic scoring for lupus nephritis: a community-based evaluation., Ann Intern Med, 119, 805, 10.7326/0003-4819-119-8-199310150-00006

Tripodo, 2010, Mast cells and Th17 cells contribute to the lymphoma-associated pro-inflammatory microenvironment of angioimmunoblastic T-cell lymphoma., Am J Pathol, 177, 792, 10.2353/ajpath.2010.091286

Metzler, 2011, Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity., Blood, 117, 953, 10.1182/blood-2010-06-290171

Jarius, 2007, Intravenous immunoglobulins contain naturally occurring antibodies that mimic antineutrophil cytoplasmic antibodies and activate neutrophils in a TNFalpha-dependent and Fc-receptor-independent way., Blood, 109, 4376, 10.1182/blood-2005-12-019604

Martinelli, 2004, Induction of genes mediating interferon-dependent extracellular trap formation during neutrophil differentiation., J Biol Chem, 279, 44123, 10.1074/jbc.M405883200

Witko-Sarsat, 2009, Neutrophils and B lymphocytes in ANCA-associated vasculitis., APMIS Suppl, 27, 10.1111/j.1600-0463.2009.02473.x

Clayton, 2003, Dendritic cell uptake of human apoptotic and necrotic neutrophils inhibits CD40, CD80, and CD86 expression and reduces allogeneic T cell responses: relevance to systemic vasculitis., Arthritis Rheum, 48, 2362, 10.1002/art.11130

Kantari, 2007, Proteinase 3, the Wegener autoantigen, is externalized during neutrophil apoptosis: evidence for a functional association with phospholipid scramblase 1 and interference with macrophage phagocytosis., Blood, 110, 4086, 10.1182/blood-2007-03-080457

Munafo, 2009, DNase I inhibits a late phase of reactive oxygen species production in neutrophils., J Innate Immun, 1, 527, 10.1159/000235860

Patry, 2001, Rats injected with syngenic rat apoptotic neutrophils develop antineutrophil cytoplasmic antibodies., J Am Soc Nephrol, 12, 1764, 10.1681/ASN.V1281764

Chin, 2000, Clinical implications of antineutrophil cytoplasmic antibody test in lupus nephritis., Am J Nephrol, 20, 57, 10.1159/000013557

Spronk, 1996, Antineutrophil cytoplasmic antibodies in systemic lupus erythematosus., Br J Rheumatol, 35, 625, 10.1093/rheumatology/35.7.625

Manolova, 2001, Antineutrophil cytoplasmic antibodies in patients with systemic lupus erythematosus: prevalence, antigen specificity, and clinical associations., Rheumatol Int, 20, 197, 10.1007/s002960100108

Galeazzi, 1998, Anti-neutrophil cytoplasmic antibodies in 566 European patients with systemic lupus erythematosus: prevalence, clinical associations and correlation with other autoantibodies. European Concerted Action on the Immunogenetics of SLE., Clin Exp Rheumatol, 16, 541

Drenkard, 1997, Vasculitis in systemic lupus erythematosus., Lupus, 6, 235, 10.1177/096120339700600304

Pradhan, 2004, Anti-neutrophil cytoplasmic antibodies (ANCA) in systemic lupus erythematosus: prevalence, clinical associations and correlation with other autoantibodies., J Assoc Physicians India, 52, 533

Steinman, 2006, Linking innate to adaptive immunity through dendritic cells., Novartis Found Symp, 279, 101, 10.1002/9780470035399.ch9

Donnelly, 2006, Impaired recognition of apoptotic neutrophils by the C1q/calreticulin and CD91 pathway in systemic lupus erythematosus., Arthritis Rheum, 54, 1543, 10.1002/art.21783

Gaipl, 2006, Inefficient clearance of dying cells and autoreactivity., Curr Top Microbiol Immunol, 305, 161

Potter, 2003, Lupus-prone mice have an abnormal response to thioglycolate and an impaired clearance of apoptotic cells., J Immunol, 170, 3223, 10.4049/jimmunol.170.6.3223

Gilligan, 1996, Antineutrophil cytoplasmic autoantibodies interact with primary granule constituents on the surface of apoptotic neutrophils in the absence of neutrophil priming., J Exp Med, 184, 2231, 10.1084/jem.184.6.2231

Abdgawad, 2012, Decreased neutrophil apoptosis in quiescent ANCA-associated systemic vasculitis., PLoS One, 7, e32439, 10.1371/journal.pone.0032439

Griffith, 2011, Cell death in the maintenance and abrogation of tolerance: the five Ws of dying cells., Immunity, 35, 456, 10.1016/j.immuni.2011.08.011

Bianchi, 2007, High-mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity., Immunol Rev, 220, 35, 10.1111/j.1600-065X.2007.00574.x

Guiducci, 2010, TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus., Nature, 465, 937, 10.1038/nature09102

Santiago-Raber, 2010, Critical role of TLR7 in the acceleration of systemic lupus erythematosus in TLR9-deficient mice., J Autoimmun, 34, 339, 10.1016/j.jaut.2009.11.001

van Timmeren, 2012, Pathogenesis of ANCA-associated vasculitis: recent insights from animal models., Curr Opin Rheumatol, 24, 8, 10.1097/BOR.0b013e32834bde57

van der Geld, 2004, B cell epitope specificity in ANCA-associated vasculitis: does it matter?, Clin Exp Immunol, 137, 451, 10.1111/j.1365-2249.2004.02572.x

Nagata, 2003, Degradation of chromosomal DNA during apoptosis., Cell Death Differ, 10, 108, 10.1038/sj.cdd.4401161

Dittmar, 2009, A novel mutation in the DNASE1 gene is related with protein instability and decreased enzyme activity in thyroid autoimmunity., J Autoimmun, 32, 7, 10.1016/j.jaut.2008.09.005

Thông tin
Thông tin xuất bản

Blood

Tập 120 Số 15

3007-3018

Thông tin tác giả