Abstract
Since the 1997 discovery that the first identified human homolog of Drosophila Toll could activate the innate immune system, the innate arm of immunity has rapidly taken on a new light as an important player in the recognition of pathogens and damaged self. The recognition of danger by dendritic cells (DC) is a crucial step in activating the adaptive immune system. Different DC express varied subsets of pattern recognition receptors (PRR), enabling both overlap and exclusivity in the recognition of danger signals by DC. PRR-mediated DC maturation and activation can be measured by changes in the surface expression of costimulatory as well as coinhibitory molecules, changes in size and shape of the DC and by their production of different cytokines.
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References
Alcantara-Hernandez M, Leylek R, Wagar LE, Engleman EG, Keler T, Marinkovich MP, Davis MM, Nolan GP, Idoyaga J (2017) High-dimensional phenotypic mapping of human dendritic cells reveals interindividual variation and tissue specialization. Immunity 47:1037–1050.e1036. https://doi.org/10.1016/j.immuni.2017.11.001
Villani AC, Satija R, Reynolds G, Sarkizova S, Shekhar K, Fletcher J, Griesbeck M, Butler A, Zheng S, Lazo S, Jardine L, Dixon D, Stephenson E, Nilsson E, Grundberg I, McDonald D, Filby A, Li W, De Jager PL, Rozenblatt-Rosen O, Lane AA, Haniffa M, Regev A, Hacohen N (2017) Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors. Science 356. https://doi.org/10.1126/science.aah4573
Medzhitov R, Preston-Hurlburt P, Janeway CA Jr (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388:394–397. https://doi.org/10.1038/41131
O’Keeffe M, Hochrein H, Vremec D, Scott B, Hertzog P, Tatarczuch L, Shortman K (2003) Dendritic cell precursor populations of mouse blood: identification of the murine homologues of human blood plasmacytoid pre-DC2 and CD11c+ DC1 precursors. Blood 101:1453–1459. https://doi.org/10.1182/blood-2002-03-0974
Mittag D, Proietto AI, Loudovaris T, Mannering SI, Vremec D, Shortman K, Wu L, Harrison LC (2011) Human dendritic cell subsets from spleen and blood are similar in phenotype and function but modified by donor health status. J Immunol (Baltimore, Md) 1950(186):6207–6217. https://doi.org/10.4049/jimmunol.1002632
Jongbloed SL, Kassianos AJ, McDonald KJ, Clark GJ, Ju X, Angel CE, Chen C-JJ, Dunbar PR, Wadley RB, Jeet V, Vulink AJE, Hart DNJ, Radford KJ (2010) Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens. J Exp Med 207:1247–1260. https://doi.org/10.1084/jem.20092140
Lauterbach H, Bathke B, Gilles S, Traidl-Hoffmann C, Luber CA, Fejer G, Freudenberg MA, Davey GM, Vremec D, Kallies A, Wu L, Shortman K, Chaplin P, Suter M, O’Keeffe M, Hochrein H (2010) Mouse CD8alpha+ DCs and human BDCA3+ DCs are major producers of IFN-lambda in response to poly IC. J Exp Med 207:2703–2717. https://doi.org/10.1084/jem.20092720
MacDonald KPA, Munster DJ, Clark GJ, Dzionek A, Schmitz J, Hart DNJ (2002) Characterization of human blood dendritic cell subsets. Blood 100:4512–4520. https://doi.org/10.1182/blood-2001-11-0097
Piccioli D, Tavarini S, Borgogni E, Steri V, Nuti S, Sammicheli C, Bardelli M, Montagna D, Locatelli F, Wack A (2007) Functional specialization of human circulating CD16 and CD1c myeloid dendritic-cell subsets. Blood 109:5371–5379. https://doi.org/10.1182/blood-2006-08-038422
Robbins SH, Walzer T, Dembélé D, Thibault C, Defays A, Bessou G, Xu H, Vivier E, Sellars M, Pierre P, Sharp FR, Chan S, Kastner P, Dalod M (2008) Novel insights into the relationships between dendritic cell subsets in human and mouse revealed by genome-wide expression profiling. Genome Biol 9:R17. https://doi.org/10.1186/gb-2008-9-1-r17
Heidkamp GF, Sander J, Lehmann CHK, Heger L, Eissing N, Baranska A, Luhr JJ, Hoffmann A, Reimer KC, Lux A, Soder S, Hartmann A, Zenk J, Ulas T, McGovern N, Alexiou C, Spriewald B, Mackensen A, Schuler G, Schauf B, Forster A, Repp R, Fasching PA, Purbojo A, Cesnjevar R, Ullrich E, Ginhoux F, Schlitzer A, Nimmerjahn F, Schultze JL, Dudziak D (2016) Human lymphoid organ dendritic cell identity is predominantly dictated by ontogeny, not tissue microenvironment. Sci Immunol 1. https://doi.org/10.1126/sciimmunol.aai7677
Sichien D, Lambrecht BN, Guilliams M, Scott CL (2017) Development of conventional dendritic cells: from common bone marrow progenitors to multiple subsets in peripheral tissues. Mucosal Immunol. https://doi.org/10.1038/mi.2017.8
Ding Y, Wilkinson A, Idris A, Fancke B, O’Keeffe M, Khalil D, Ju X, Lahoud MH, Caminschi I, Shortman K, Rodwell R, Vuckovic S, Radford KJ (2014) FLT3-ligand treatment of humanized mice results in the generation of large numbers of CD141+ and CD1c+ dendritic cells in vivo. J Immunol 192:1982–1989. https://doi.org/10.4049/jimmunol.1302391
Minoda Y, Virshup I, Leal Rojas I, Haigh O, Wong Y, Miles JJ, Wells CA, Radford KJ (2017) Human CD141(+) dendritic cell and CD1c(+) dendritic cell undergo concordant early genetic programming after activation in humanized mice in vivo. Front Immunol 8:1419. https://doi.org/10.3389/fimmu.2017.01419
Pearson FE, Chang K, Minoda Y, Rojas IML, Haigh OL, Daraj G, Tullett KM, Radford KJ (2018) Activation of human CD141(+) and CD1c(+) dendritic cells in vivo with combined TLR3 and TLR7/8 ligation. Immunol Cell Biol 96:390–400. https://doi.org/10.1111/imcb.12009
Macri C, Pang ES, Patton T, O’Keeffe M (2017) Dendritic cell subsets. Semin Cell Dev Biol. https://doi.org/10.1016/j.semcdb.2017.12.009
O’Keeffe M, Mok WH, Radford KJ (2015) Human dendritic cell subsets and function in health and disease. Cell Mol Life Sci 72:4309–4325. https://doi.org/10.1007/s00018-015-2005-0
O’Keeffe M (2012) Conventional dendritic cells may be ideal targets for vaccine strategies in the aged. Immunol Cell Biol 90:665–666. https://doi.org/10.1038/icb.2012.16
Naik SH, O’Keeffe M, Proietto A, Shortman HH, Wu L (2010) CD8+, CD8-, and plasmacytoid dendritic cell generation in vitro using flt3 ligand. Methods Mol Biol 595:167–176. https://doi.org/10.1007/978-1-60761-421-0_10
Duthie MS, Windish HP, Fox CB, Reed SG (2011) Use of defined TLR ligands as adjuvants within human vaccines. Immunol Rev 239:178–196. https://doi.org/10.1111/j.1600-065X.2010.00978.x
Luber CA, Cox J, Lauterbach H, Fancke B, Selbach M, Tschopp J, Akira S, Wiegand M, Hochrein H, O’Keeffe M, Mann M (2010) Quantitative proteomics reveals subset-specific viral recognition in dendritic cells. Immunity 32:279–289. https://doi.org/10.1016/j.immuni.2010.01.013
Hochrein H, O’Keeffe M, Luft T, Vandenabeele S, Grumont RJ, Maraskovsky E, Shortman K (2000) Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12 production by mouse and human dendritic cells. J Exp Med 192:823–833
Vremec D, O’Keeffe M, Wilson A, Ferrero I, Koch U, Radtke F, Scott B, Hertzog P, Villadangos J, Shortman K (2011) Factors determining the spontaneous activation of splenic dendritic cells in culture. Innate Immun 17:338–352. https://doi.org/10.1177/1753425910371396
Vremec D, Hansen J, Strasser A, Acha-Orbea H, Zhan Y, O’Keeffe M, Shortman K (2015) Maintaining dendritic cell viability in culture. Mol Immunol 63:264–267. https://doi.org/10.1016/j.molimm.2014.07.011
O’Keeffe M, Grumont RJ, Hochrein H, Fuchsberger M, Gugasyan R, Vremec D, Shortman K, Gerondakis S (2005) Distinct roles for the NF-kappaB1 and c-Rel transcription factors in the differentiation and survival of plasmacytoid and conventional dendritic cells activated by TLR-9 signals. Blood 106:3457–3464. https://doi.org/10.1182/blood-2004-12-4965
Asselin-Paturel C, Boonstra A, Dalod M, Durand I, Yessaad N, Dezutter-Dambuyant C, Vicari A, O’Garra A, Biron C, Brière F, Trinchieri G (2001) Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology. Nat Immunol 2:1144–1150. https://doi.org/10.1038/ni736
Asselin-Paturel C, Brizard G, Chemin K, Boonstra A, Garra A, Vicari A, Trinchieri G (2005) Type I interferon dependence of plasmacytoid dendritic cell activation and migration. J Exp Med 201:1157
Fuertes Marraco SA, Scott CL, Bouillet P, Ives A, Masina S, Vremec D, Jansen ES, O’Reilly LA, Schneider P, Fasel N, Shortman K, Strasser A, Acha-Orbea H (2011) Type I interferon drives dendritic cell apoptosis via multiple BH3-only proteins following activation by PolyIC in vivo. PLoS One 6:e20189. https://doi.org/10.1371/journal.pone.0020189
Acknowledgments
This work was supported by an NHMRC Senior Research Fellowship 1077633 (M.O.K.), and NHMRC Project grants 1085934; 1002903 to M.O.K. and K.R.
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Macri, C., Fancke, B., Radford, K.J., O’Keeffe, M. (2019). Monitoring Dendritic Cell Activation and Maturation. In: van Endert, P. (eds) Antigen Processing. Methods in Molecular Biology, vol 1988. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9450-2_28
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DOI: https://doi.org/10.1007/978-1-4939-9450-2_28
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