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Influence of Aging on Antigen Uptake and Cytokine Production by Dendritic Cells

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Handbook of Immunosenescence

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Abstract

In recent years, the proportion of older adults has been increasing dramatically, in parallel to an increase in life expectancy. The effect of age over immune system includes alterations in the cells involved in innate and adaptive immunity that negatively impact the health of older adults. Therefore, it is expected an increased susceptibility to a wide range of pathologies, including cardiovascular diseases, osteoporosis, Alzheimer’s disease, diabetes, cancer, autoimmune disorders, infectious diseases, and poorer vaccine responses in this population. Recent evidences suggest that the efficiency of cross-presentation from dendritic cells (DCs) can be influenced by aging, altering the adaptive immune response as well as both nonadaptive and humoral immunities. DCs are key members of antigen-presenting cells of the immune system and playing a decisive role in development of immune response against infection, foreign material, commensals, or tissue damage. These cells have the ability to take up antigen, process it for presentation on MHC-I or II, and effectively activate and polarize naïve T cells by production of cytokines. This chapter focuses on the most recent 16 years of studies on the effects of aging on the antigen uptake and cytokine production by DCs. Indeed, many authors reported alterations in number, phenotype, and distribution of DC subtypes. However, few and inconclusive studies have focused on age-related alterations in uptake by DCs. Finally, already, there is some consensus about alterations in cytokine production by these cells from aged donors, depending on the DC subtype.

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References

  • Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F (2007) Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 8(9):942–949

    Article  CAS  Google Scholar 

  • Acton SE, Reis e Sousa C (2016) Dendritic cells in remodeling of lymph nodes during immune responses. Immunol Rev 271(1):221–229

    Article  CAS  Google Scholar 

  • Agrawal A (2013) Mechanisms and implications of age-associated impaired innate interferon secretion by dendritic cells: a mini-review. Gerontology 59(5):421–426

    Article  Google Scholar 

  • Agrawal A, Gupta S (2011) Impact of aging on dendritic cell functions in humans. Ageing Res Rev 10(3):336–345

    Article  CAS  Google Scholar 

  • Agrawal A, Tay J, Ton S, Agrawal S, Gupta S (2009) Increased reactivity of dendritic cells from aged subjects to self-antigen, the human DNA. J Immunol 182(2):1138–1145

    Article  CAS  Google Scholar 

  • Agrawal A, Agrawal S, Cao JN, Su H, Osann K, Gupta S (2007) Altered innate immune functioning of dendritic cells in elderly humans: a role of phosphoinositide 3-kinase-signaling pathway. J Immunol 178(11):6912–6922

    Article  CAS  Google Scholar 

  • Bauer ME, Fuente M (2016) The role of oxidative and inflammatory stress and persistent viral infections in immunosenescence. Mech Ageing Dev 158:27–37

    Article  CAS  Google Scholar 

  • Boren E, Gershwin ME (2004) Inflamm-aging: autoimmunity, and the immune-risk phenotype. Autoimmun Rev 3(5):401–406

    Article  CAS  Google Scholar 

  • Bufan B, Stojić-Vukanić Z, Djikić J, Kosec D, Pilipović I, Nacka-Aleksić M et al (2015) Aging impairs endocytic capacity of splenic dendritic cells from dark agouti rats and alters their response to TLR4 stimulation. Acta Vet-Beograd 65(1):30–55

    Article  Google Scholar 

  • Canaday DH, Amponsah NA, Jones L, Tisch DJ, Hornick TR, Ramachandra L (2010) Influenza-induced production of interferon-alpha is defective in geriatric individuals. J Clin Immunol 30(3):373–383

    Article  CAS  Google Scholar 

  • Chai LY, Netea MG, Vonk AG, Kullberg BJ (2009) Fungal strategies for overcoming host innate immune response. Med Mycol 47(3):227–236

    Article  CAS  Google Scholar 

  • Chougnet CA, Thacker RI, Shehata HM, Hennies CM, Lehn MA, Lages CS et al (2015) Loss of phagocytic and antigen cross-presenting capacity in aging dendritic cells is associated with mitochondrial dysfunction. J Immunol 195(6):2624–2632

    Article  CAS  Google Scholar 

  • Ciaramella A, Spalletta G, Bizzoni F, Salani F, Caltagirone C, Bossù P (2011) Effect of age on surface molecules and cytokine expression in human dendritic cells. Cell Immunol 269(2):82–89

    Article  CAS  Google Scholar 

  • Compté N, Zouaoui Boudjeltia K, Vanhaeverbeek M, De Breucker S, Tassignon J, Trelcat A et al (2013) Frailty in old age is associated with decreased interleukin-12/23 production in response to toll-like receptor ligation. PLoS One 8(6):e65325

    Article  Google Scholar 

  • Della Bella S, Bierti L, Presicce P, Arienti R, Valenti M, Saresella M et al (2007) Peripheral blood dendritic cells and monocytes are differently regulated in the elderly. Clin Immunol 122(2):220–228

    Article  CAS  Google Scholar 

  • El Mezayen R, El Gazzar M, Myer R, High KP (2009) Aging-dependent upregulation of IL-23p19 gene expression in dendritic cells is associated with differential transcription factor binding and histone modifications. Aging Cell 8(5):553–565

    Article  Google Scholar 

  • Elliot AJ, Fleming DM (2008) Influenza and respiratory syncytial virus in the elderly. Expert Rev Vaccines 7(2):249–258

    Article  Google Scholar 

  • Ershler WB, Longo DL (1997) Aging and cancer: issues of basic and clinical science. J Natl Cancer Inst 89(20):1489–1497

    Article  CAS  Google Scholar 

  • Fink SL, Cookson BT (2005) Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect Immun 73(4):1907–1916

    Article  CAS  Google Scholar 

  • Fitzgerald-Bocarsly P, Dai J, Singh S (2008) Plasmacytoid dendritic cells and type I IFN: 50 years of convergent history. Cytokine Growth Factor Rev 19(1):3–19

    Article  CAS  Google Scholar 

  • Franceschi C, Campisi J (2014) Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 69(Suppl 1):S4–S9

    Article  Google Scholar 

  • García-Sastre A, Biron CA (2006) Type 1 interferons and the virus-host relationship: a lesson in détente. Science 312(5775):879–882

    Article  Google Scholar 

  • Glaser R, MacCallum RC, Laskowski BF, Malarkey WB, Sheridan JF, Kiecolt-Glaser JK (2001) Evidence for a shift in the Th-1 to Th-2 cytokine response associated with chronic stress and aging. J Gerontol A Biol Sci Med Sci 56(8):M477–M482

    Article  CAS  Google Scholar 

  • Grolleau-Julius A, Harning EK, Abernathy LM, Yung RL (2008) Impaired dendritic cell function in aging leads to defective antitumor immunity. Cancer Res 68(15):6341–6349

    Article  CAS  Google Scholar 

  • Grubeck-Loebenstein B, Della Bella S, Iorio AM, Michel JP, Pawelec G, Solana R (2009) Immunosenescence and vaccine failure in the elderly. Aging Clin Exp Res 21(3):201–209

    Article  CAS  Google Scholar 

  • Guicciardi ME, Gores GJ (2005) Apoptosis: a mechanism of acute and chronic liver injury. Gut 54(7):1024–1033

    Article  CAS  Google Scholar 

  • Guilliams M, Ginhoux F, Jakubzick C, Naik SH, Onai N, Schraml BU et al (2014) Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat Rev Immunol 14(8):571–578

    Article  CAS  Google Scholar 

  • Gupta S (2014) Role of dendritic cells in innate and adaptive immune response in human aging. Exp Gerontol 54:47–52

    Article  CAS  Google Scholar 

  • Hainz U, Jenewein B, Asch E, Pfeiffer KP, Berger P, Grubeck-Loebenstein B (2005) Insufficient protection for healthy elderly adults by tetanus and TBE vaccines. Vaccine 23(25):3232–3235

    Article  Google Scholar 

  • Hiscox S, Jiang WG (1997) Interleukin-12, an emerging anti-tumour cytokine. In Vivo 11(2):125–132

    CAS  PubMed  Google Scholar 

  • Jiang S, Li P (2016) Current development in elderly comprehensive assessment and research methods. Biomed Res Int 2016:3528248

    PubMed  PubMed Central  Google Scholar 

  • Jiang M, Österlund P, Fagerlund R, Rios DN, Hoffmann A, Poranen MM et al (2015) MAP kinase p38α regulates type III interferon (IFN-λ1) gene expression in human monocyte-derived dendritic cells in response to RNA stimulation. J Leukoc Biol 97(2):307–320

    Article  Google Scholar 

  • Jing Y, Shaheen E, Drake RR, Chen N, Gravenstein S, Deng Y (2009) Aging is associated with a numerical and functional decline in plasmacytoid dendritic cells, whereas myeloid dendritic cells are relatively unaltered in human peripheral blood. Hum Immunol 70(10):777–784

    Article  CAS  Google Scholar 

  • Kaml M, Weiskirchner I, Keller M, Luft T, Hoster E, Hasford J et al (2006) Booster vaccination in the elderly: their success depends on the vaccine type applied earlier in life as well as on pre-vaccination antibody titers. Vaccine 24(47–48):6808–6811

    Article  CAS  Google Scholar 

  • Kapsenberg ML (2003) Dendritic-cell control of pathogen-driven T-cell polarization. Nat Rev Immunol 3(12):984–993

    Article  CAS  Google Scholar 

  • Kauffman CA (2001) Fungal infections in older adults. Clin Infect Dis 33(4):550–555

    Article  CAS  Google Scholar 

  • Koido S (2016) Dendritic-tumor fusion cell-based cancer vaccines. Int J Mol Sci 17(6)

    Article  Google Scholar 

  • Koltsida O, Hausding M, Stavropoulos A, Koch S, Tzelepis G, Ubel C et al (2011) IL-28A (IFN-λ2) modulates lung DC function to promote Th1 immune skewing and suppress allergic airway disease. EMBO Mol Med 3(6):348–361

    Article  CAS  Google Scholar 

  • Lande R, Gilliet M (2010) Plasmacytoid dendritic cells: key players in the initiation and regulation of immune responses. Ann N Y Acad Sci 1183:89–103

    Article  CAS  Google Scholar 

  • Lung TL, Saurwein-Teissl M, Parson W, Schönitzer D, Grubeck-Loebenstein B (2000) Unimpaired dendritic cells can be derived from monocytes in old age and can mobilize residual function in senescent T cells. Vaccine 18(16):1606–1612

    Article  CAS  Google Scholar 

  • Ma Y, Shurin GV, Peiyuan Z, Shurin MR (2013) Dendritic cells in the cancer microenvironment. J Cancer 4(1):36–44

    Article  CAS  Google Scholar 

  • Macatonia SE, Hosken NA, Litton M, Vieira P, Hsieh CS, Culpepper JA et al (1995) Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells. J Immunol 154(10):5071–5079

    CAS  PubMed  Google Scholar 

  • Martin SJ (2016) Cell death and inflammation: the case for IL-1 family cytokines as the canonical DAMPs of the immune system. FEBS J 283:2599–2615

    Article  CAS  Google Scholar 

  • McGovern N, Chan JK, Ginhoux F (2015) Dendritic cells in humans – from fetus to adult. Int Immunol 27(2):65–72

    Article  CAS  Google Scholar 

  • Mildner A, Jung S (2014) Development and function of dendritic cell subsets. Immunity 40(5):642–656

    Article  CAS  Google Scholar 

  • Moretto MM, Lawlor EM, Khan IA (2008) Aging mice exhibit a functional defect in mucosal dendritic cell response against an intracellular pathogen. J Immunol 181(11):7977–7984

    Article  CAS  Google Scholar 

  • Nascimento MPP, Lara VS (2011) Dendritic cells in immunosenescence. Annu Rev Biomed Sci 13:9–16

    CAS  Google Scholar 

  • Nascimento MPP, Pinke KH, Penitenti M, Ikoma MR, Lara VS (2015) Aging does not affect the ability of human monocyte-derived dendritic cells to phagocytose Candida albicans. Aging Clin Exp Res 27(6):785–789

    Article  Google Scholar 

  • Oliver JM, Berlin RD, Davis BH (1984) Use of horseradish peroxidase and fluorescent dextrans to study fluid pinocytosis in leukocytes. Methods Enzymol 108:336–347

    Article  CAS  Google Scholar 

  • Opitz B, Rejaibi A, Dauber B, Eckhard J, Vinzing M, Schmeck B et al (2007) IFNbeta induction by influenza A virus is mediated by RIG-I which is regulated by the viral NS1 protein. Cell Microbiol 9(4):930–938

    Article  CAS  Google Scholar 

  • Panda A, Qian F, Mohanty S, van Duin D, Newman FK, Zhang L et al (2010) Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response. J Immunol 184(5):2518–2527

    Article  CAS  Google Scholar 

  • Paula C, Motta A, Schmitz C, Nunes CP, Souza AP, Bonorino C (2009) Alterations in dendritic cell function in aged mice: potential implications for immunotherapy design. Biogerontology 10(1):13–25

    Article  CAS  Google Scholar 

  • Pera A, Campos C, López N, Hassouneh F, Alonso C, Tarazona R et al (2015) Immunosenescence: implications for response to infection and vaccination in older people. Maturitas 82(1):50–55

    Article  CAS  Google Scholar 

  • Pereira LF, de Souza AP, Borges TJ, Bonorino C (2011) Impaired in vivo CD4+ T cell expansion and differentiation in aged mice is not solely due to T cell defects: decreased stimulation by aged dendritic cells. Mech Ageing Dev 132(4):187–194

    Article  CAS  Google Scholar 

  • Reboulet RA, Hennies CM, Garcia Z, Nierkens S, Janssen EM (2010) Prolonged antigen storage endows merocytic dendritic cells with enhanced capacity to prime anti-tumor responses in tumor-bearing mice. J Immunol 185(6):3337–3347

    Article  CAS  Google Scholar 

  • Reis e Sousa C (2006) Dendritic cells in a mature age. Nat Rev Immunol 6(6):476–483

    Article  CAS  Google Scholar 

  • Rink L, Cakman I, Kirchner H (1998) Altered cytokine production in the elderly. Mech Ageing Dev 102(2–3):199–209

    Article  CAS  Google Scholar 

  • Romagnani C, Chiesa MD, Kahler S, Moewes B, Radbruch A, Moretta L et al. (2005) Activation of human NK cells by plasmacytoid dendritic cells and its modulation by CD4+ T helper cells and CD4+ CD25hi T regulatory cells. Eur J Immunol 35: 2452–2458.

    Article  CAS  Google Scholar 

  • Sauter B, Albert ML, Francisco L, Larsson M, Somersan S, Bhardwaj N (2000) Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med 191(3):423–434

    Article  CAS  Google Scholar 

  • Sharma S, Dominguez AL, Lustgarten J (2006) Aging affect the anti-tumor potential of dendritic cell vaccination, but it can be overcome by co-stimulation with anti-OX40 or anti-4-1BB. Exp Gerontol 41(1):78–84

    Article  CAS  Google Scholar 

  • Shodell M, Siegal FP (2002) Circulating, interferon-producing plasmacytoid dendritic cells decline during human ageing. Scand J Immunol 56(5):518–521

    Article  CAS  Google Scholar 

  • Shortman K, Sathe P, Vremec D, Naik S, O’Keeffe M (2013) Plasmacytoid dendritic cell development. Adv Immunol 120:105–126

    Article  CAS  Google Scholar 

  • Sridharan A, Esposo M, Kaushal K, Tay J, Osann K, Agrawal S et al (2011) Age-associated impaired plasmacytoid dendritic cell functions lead to decreased CD4 and CD8 T cell immunity. Age (Dordr) 33(3):363–376

    Article  CAS  Google Scholar 

  • Stojić-Vukanić Z, Bufan B, Arsenović-Ranin N, Kosec D, Pilipović I, Perišić Nanut M et al (2013) Aging affects AO rat splenic conventional dendritic cell subset composition, cytokine synthesis and T-helper polarizing capacity. Biogerontology 14(4):443–459

    Article  Google Scholar 

  • Stout-Delgado HW, Yang X, Walker WE, Tesar BM, Goldstein DR (2008) Aging impairs IFN regulatory factor 7 up-regulation in plasmacytoid dendritic cells during TLR9 activation. J Immunol 181(10):6747–6756

    Article  CAS  Google Scholar 

  • Ullrich E, Ménard C, Flament C, Terme M, Mignot G, Bonmort M et al (2008) Dendritic cells and innate defense against tumor cells. Cytokine Growth Factor Rev 19(1):79–92

    Article  CAS  Google Scholar 

  • Wilson NJ, Boniface K, Chan JR, McKenzie BS, Blumenschein WM, Mattson JD et al (2007) Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 8(9):950–957

    Article  CAS  Google Scholar 

  • Wong CP, Magnusson KR, Ho E (2010) Aging is associated with altered dendritic cells subset distribution and impaired proinflammatory cytokine production. Exp Gerontol 45(2):163–169

    Article  CAS  Google Scholar 

  • Xu YP, Qi RQ, Chen W, Shi Y, Cui ZZ, Gao XH et al (2012) Aging affects epidermal Langerhans cell development and function and alters their miRNA gene expression profile. Aging (Albany NY) 4(11):742–754

    Article  CAS  Google Scholar 

  • You J, Dong H, Mann ER, Knight SC, Yaqoob P (2013) Ageing impairs the T cell response to dendritic cells. Immunobiology 218(8):1077–1084

    Article  CAS  Google Scholar 

  • Zhou L, Chong MM, Littman DR (2009) Plasticity of CD4+ T cell lineage differentiation. Immunity 30(5):646–655

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil – process number 307232/2015-8) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Brazil – process number 09/17889-5 and 10/15271-1).

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Authors and Affiliations

  1. Department of Surgery, Stomatology, Pathology and Radiology, Bauru School of Dentistry, University of São Paulo (USP), Bauru, SP, Brazil

    Karen Henriette Pinke, Heliton Gustavo de Lima & Vanessa Soares Lara

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  1. Karen Henriette Pinke
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  2. Heliton Gustavo de Lima
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  3. Vanessa Soares Lara
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Correspondence to Vanessa Soares Lara .

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Editors and Affiliations

  1. Division of Geriatrics Research Center on Aging, University of Sherbrooke Department of Medicine, Sherbrooke, QC, Canada

    Tamas Fulop

  2. Department of Experimental Pathology, University of Bologna, Bologna, Italy

    Claudio Franceschi

  3. Institute for Health and Life Sciences, Tokyo, Japan

    Katsuiku Hirokawa

  4. Center for Medical Research, University of Tübingen, Tübingen, Germany

    Graham Pawelec

Section Editor information

  1. Research Center on Aging, Department of Medicine, Immunology Graduate Programme, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada

    Tamas Fulop

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Pinke, K.H., de Lima, H.G., Lara, V.S. (2019). Influence of Aging on Antigen Uptake and Cytokine Production by Dendritic Cells. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook of Immunosenescence. Springer, Cham. https://doi.org/10.1007/978-3-319-99375-1_93

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