Global analyses revealed age‐related alterations in innate immune responses after stimulation of pathogen recognition receptors

Summary Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive B and T cells are well documented, but the effect of aging on innate immunity re...

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Published inAging cell Vol. 14; no. 3; pp. 421 - 432
Main Authors Metcalf, Talibah U., Cubas, Rafael A., Ghneim, Khader, Cartwright, Michael J., Grevenynghe, Julien Van, Richner, Justin M., Olagnier, David P., Wilkinson, Peter A., Cameron, Mark J., Park, Byung S., Hiscott, John B., Diamond, Michael S., Wertheimer, Anne M., Nikolich‐Zugich, Janko, Haddad, Elias K.
Format Journal Article
LanguageEnglish
Published England John Wiley & Sons, Inc 01.06.2015
BlackWell Publishing Ltd
Subjects
Adaptive Immunity - genetics
Adult
Aged
Aged, 80 and over
Aging
B cells
B-Lymphocytes - immunology
Biological response modifiers
Chemokines - metabolism
Comparative analysis
Cytokines - metabolism
Dendritic cells
Dendritic Cells - immunology
Disease susceptibility
Health aspects
Humans
Immune response
Immune system
Immunity, Innate - immunology
immunosenescence
Immunotherapy
innate immune agonists
innate immunity
Interferon
interferon signaling
Leukocytes, Mononuclear - metabolism
Lymphocyte Activation - genetics
Lymphocytes
Monocytes - immunology
Original
pattern recognition receptors
peripheral blood mononuclear cells
T cells
T-Lymphocytes - immunology
Vaccines
Young Adult
pattern recognition receptors
peripheral blood mononuclear cells
immunosenescence
interferon signaling
innate immunity
innate immune agonists
Online AccessGet full text
ISSN1474-9718
1474-9728
1474-9726
1474-9726
DOI10.1111/acel.12320

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Abstract Summary Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive B and T cells are well documented, but the effect of aging on innate immunity remains incompletely understood. Using a heterogeneous population of peripheral blood mononuclear cells (PBMCs), we first undertook transcriptional profiling and found that PBMCs isolated from old individuals (≥ 65 years) exhibited a delayed and altered response to stimulation with TLR4, TLR7/8, and RIG‐I agonists compared to cells obtained from adults (≤ 40 years). This delayed response to innate immune agonists resulted in the reduced production of pro‐inflammatory and antiviral cytokines and chemokines including TNFα, IL‐6, IL‐1β, IFNα, IFNγ, CCL2, and CCL7. While the major monocyte and dendritic cell subsets did not change numerically with aging, activation of specific cell types was altered. PBMCs from old subjects also had a lower frequency of CD40+ monocytes, impaired up‐regulation of PD‐L1 on monocytes and T cells, and increased expression of PD‐L2 and B7‐H4 on B cells. The defective immune response to innate agonists adversely affected adaptive immunity as TLR‐stimulated PBMCs (minus CD3 T cells) from old subjects elicited significantly lower levels of adult T‐cell proliferation than those from adult subjects in an allogeneic mixed lymphocyte reaction (MLR). Collectively, these age‐associated changes in cytokine, chemokine and interferon production, as well as co‐stimulatory protein expression could contribute to the blunted memory B‐ and T‐cell immune responses to vaccines and infections.
AbstractList Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive B and T cells are well documented, but the effect of aging on innate immunity remains incompletely understood. Using a heterogeneous population of peripheral blood mononuclear cells (PBMCs), we first undertook transcriptional profiling and found that PBMCs isolated from old individuals ( greater than or equal to 65 years) exhibited a delayed and altered response to stimulation with TLR4, TLR7/8, and RIG-I agonists compared to cells obtained from adults ( less than or equal to 40 years). This delayed response to innate immune agonists resulted in the reduced production of pro-inflammatory and antiviral cytokines and chemokines including TNF alpha , IL-6, IL-1 beta , IFN alpha , IFN gamma , CCL2, and CCL7. While the major monocyte and dendritic cell subsets did not change numerically with aging, activation of specific cell types was altered. PBMCs from old subjects also had a lower frequency of CD40+ monocytes, impaired up-regulation of PD-L1 on monocytes and T cells, and increased expression of PD-L2 and B7-H4 on B cells. The defective immune response to innate agonists adversely affected adaptive immunity as TLR-stimulated PBMCs (minus CD3 T cells) from old subjects elicited significantly lower levels of adult T-cell proliferation than those from adult subjects in an allogeneic mixed lymphocyte reaction (MLR). Collectively, these age-associated changes in cytokine, chemokine and interferon production, as well as co-stimulatory protein expression could contribute to the blunted memory B- and T-cell immune responses to vaccines and infections.
Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive B and T cells are well documented, but the effect of aging on innate immunity remains incompletely understood. Using a heterogeneous population of peripheral blood mononuclear cells (PBMCs), we first undertook transcriptional profiling and found that PBMCs isolated from old individuals (≥ 65 years) exhibited a delayed and altered response to stimulation with TLR4, TLR7/8, and RIG-I agonists compared to cells obtained from adults (≤ 40 years). This delayed response to innate immune agonists resulted in the reduced production of pro-inflammatory and antiviral cytokines and chemokines including TNFα, IL-6, IL-1β, IFNα, IFNγ, CCL2, and CCL7. While the major monocyte and dendritic cell subsets did not change numerically with aging, activation of specific cell types was altered. PBMCs from old subjects also had a lower frequency of CD40+ monocytes, impaired up-regulation of PD-L1 on monocytes and T cells, and increased expression of PD-L2 and B7-H4 on B cells. The defective immune response to innate agonists adversely affected adaptive immunity as TLR-stimulated PBMCs (minus CD3 T cells) from old subjects elicited significantly lower levels of adult T-cell proliferation than those from adult subjects in an allogeneic mixed lymphocyte reaction (MLR). Collectively, these age-associated changes in cytokine, chemokine and interferon production, as well as co-stimulatory protein expression could contribute to the blunted memory B- and T-cell immune responses to vaccines and infections.
Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive B and T cells are well documented, but the effect of aging on innate immunity remains incompletely understood. Using a heterogeneous population of peripheral blood mononuclear cells (PBMCs), we first undertook transcriptional profiling and found that PBMCs isolated from old individuals (≥ 65 years) exhibited a delayed and altered response to stimulation with TLR4, TLR7/8, and RIG-I agonists compared to cells obtained from adults (≤ 40 years). This delayed response to innate immune agonists resulted in the reduced production of pro-inflammatory and antiviral cytokines and chemokines including TNFα, IL-6, IL-1β, IFNα, IFNγ, CCL2, and CCL7. While the major monocyte and dendritic cell subsets did not change numerically with aging, activation of specific cell types was altered. PBMCs from old subjects also had a lower frequency of CD40+ monocytes, impaired up-regulation of PD-L1 on monocytes and T cells, and increased expression of PD-L2 and B7-H4 on B cells. The defective immune response to innate agonists adversely affected adaptive immunity as TLR-stimulated PBMCs (minus CD3 T cells) from old subjects elicited significantly lower levels of adult T-cell proliferation than those from adult subjects in an allogeneic mixed lymphocyte reaction (MLR). Collectively, these age-associated changes in cytokine, chemokine and interferon production, as well as co-stimulatory protein expression could contribute to the blunted memory B- and T-cell immune responses to vaccines and infections.
Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive B and T cells are well documented, but the effect of aging on innate immunity remains incompletely understood. Using a heterogeneous population of peripheral blood mononuclear cells ( PBMC s), we first undertook transcriptional profiling and found that PBMC s isolated from old individuals (≥ 65 years) exhibited a delayed and altered response to stimulation with TLR 4, TLR 7/8, and RIG ‐I agonists compared to cells obtained from adults (≤ 40 years). This delayed response to innate immune agonists resulted in the reduced production of pro‐inflammatory and antiviral cytokines and chemokines including TNF α, IL ‐6, IL ‐1β, IFN α, IFN γ, CCL 2, and CCL 7. While the major monocyte and dendritic cell subsets did not change numerically with aging, activation of specific cell types was altered. PBMC s from old subjects also had a lower frequency of CD 40+ monocytes, impaired up‐regulation of PD ‐L1 on monocytes and T cells, and increased expression of PD ‐L2 and B7‐H4 on B cells. The defective immune response to innate agonists adversely affected adaptive immunity as TLR ‐stimulated PBMC s (minus CD 3 T cells) from old subjects elicited significantly lower levels of adult T‐cell proliferation than those from adult subjects in an allogeneic mixed lymphocyte reaction ( MLR ). Collectively, these age‐associated changes in cytokine, chemokine and interferon production, as well as co‐stimulatory protein expression could contribute to the blunted memory B‐ and T‐cell immune responses to vaccines and infections.
Summary Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive B and T cells are well documented, but the effect of aging on innate immunity remains incompletely understood. Using a heterogeneous population of peripheral blood mononuclear cells (PBMCs), we first undertook transcriptional profiling and found that PBMCs isolated from old individuals (≥ 65 years) exhibited a delayed and altered response to stimulation with TLR4, TLR7/8, and RIG‐I agonists compared to cells obtained from adults (≤ 40 years). This delayed response to innate immune agonists resulted in the reduced production of pro‐inflammatory and antiviral cytokines and chemokines including TNFα, IL‐6, IL‐1β, IFNα, IFNγ, CCL2, and CCL7. While the major monocyte and dendritic cell subsets did not change numerically with aging, activation of specific cell types was altered. PBMCs from old subjects also had a lower frequency of CD40+ monocytes, impaired up‐regulation of PD‐L1 on monocytes and T cells, and increased expression of PD‐L2 and B7‐H4 on B cells. The defective immune response to innate agonists adversely affected adaptive immunity as TLR‐stimulated PBMCs (minus CD3 T cells) from old subjects elicited significantly lower levels of adult T‐cell proliferation than those from adult subjects in an allogeneic mixed lymphocyte reaction (MLR). Collectively, these age‐associated changes in cytokine, chemokine and interferon production, as well as co‐stimulatory protein expression could contribute to the blunted memory B‐ and T‐cell immune responses to vaccines and infections.
Summary Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive B and T cells are well documented, but the effect of aging on innate immunity remains incompletely understood. Using a heterogeneous population of peripheral blood mononuclear cells (PBMCs), we first undertook transcriptional profiling and found that PBMCs isolated from old individuals (≥ 65 years) exhibited a delayed and altered response to stimulation with TLR4, TLR7/8, and RIG-I agonists compared to cells obtained from adults (≤ 40 years). This delayed response to innate immune agonists resulted in the reduced production of pro-inflammatory and antiviral cytokines and chemokines including TNF[alpha], IL-6, IL-1[beta], IFN[alpha], IFN[gamma], CCL2, and CCL7. While the major monocyte and dendritic cell subsets did not change numerically with aging, activation of specific cell types was altered. PBMCs from old subjects also had a lower frequency of CD40+ monocytes, impaired up-regulation of PD-L1 on monocytes and T cells, and increased expression of PD-L2 and B7-H4 on B cells. The defective immune response to innate agonists adversely affected adaptive immunity as TLR-stimulated PBMCs (minus CD3 T cells) from old subjects elicited significantly lower levels of adult T-cell proliferation than those from adult subjects in an allogeneic mixed lymphocyte reaction (MLR). Collectively, these age-associated changes in cytokine, chemokine and interferon production, as well as co-stimulatory protein expression could contribute to the blunted memory B- and T-cell immune responses to vaccines and infections.
Audience Academic
Author Nikolich‐Zugich, Janko
Cameron, Mark J.
Hiscott, John B.
Grevenynghe, Julien Van
Diamond, Michael S.
Haddad, Elias K.
Cubas, Rafael A.
Metcalf, Talibah U.
Richner, Justin M.
Ghneim, Khader
Wilkinson, Peter A.
Olagnier, David P.
Cartwright, Michael J.
Park, Byung S.
Wertheimer, Anne M.
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  organization: Vaccine and Gene Therapy Institute of Florida
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  givenname: Rafael A.
  surname: Cubas
  fullname: Cubas, Rafael A.
  organization: Vaccine and Gene Therapy Institute of Florida
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  surname: Ghneim
  fullname: Ghneim, Khader
  organization: Case Western Reserve University
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  organization: Vaccine and Gene Therapy Institute of Florida
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  surname: Grevenynghe
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  organization: Oregon Health and Science University
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  organization: Vaccine and Gene Therapy Institute of Florida
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  givenname: Michael S.
  surname: Diamond
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  organization: University of Arizona College of Medicine
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  surname: Haddad
  fullname: Haddad, Elias K.
  organization: Vaccine and Gene Therapy Institute of Florida
BackLink https://www.ncbi.nlm.nih.gov/pubmed/25728020$$D View this record in MEDLINE/PubMed
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Cites_doi 10.1186/1471-2172-11-30
10.1086/516788
10.1016/j.jaci.2009.07.008
10.1016/j.humimm.2009.07.005
10.1093/geront/10.1_Part_1.20
10.1111/j.1474-9726.2012.00851.x
10.1093/bioinformatics/btn615
10.1016/S0047-6374(00)00204-9
10.1016/j.cellimm.2012.01.001
10.1385/IR:29:1-3:113
10.1111/j.2517-6161.1995.tb02031.x
10.1002/eji.1830230950
10.1084/jem.192.7.1027
10.1016/j.mad.2006.01.014
10.1084/jem.20082292
10.1016/j.arr.2010.10.007
10.1038/icb.2013.77
10.1016/S1074-7613(03)00208-5
10.1016/j.coi.2005.07.013
10.1016/S0047-6374(03)00013-7
10.1128/JVI.00618-08
10.1016/j.smim.2012.04.008
10.4049/jimmunol.178.2.970
10.4049/jimmunol.0901022
10.1016/S0047-6374(02)00077-5
10.1007/BF00320399
10.1007/0-387-29362-0_23
10.1046/j.1532-5415.2003.51465.x
10.1111/j.1474-9726.2011.00759.x
10.1016/S0047-6374(00)00200-1
10.1038/75556
10.1016/S1473-3099(02)00437-1
10.1186/1471-2172-14-45
10.1038/nprot.2008.211
10.1016/j.it.2009.05.004
10.1371/journal.ppat.1003298
10.1186/gb-2004-5-10-r80
10.1038/ni.2067
10.1016/j.transproceed.2012.01.096
10.1128/JVI.79.21.13350-13361.2005
10.1186/1471-2318-13-64
10.1016/j.imbio.2013.02.002
10.1073/pnas.0506580102
10.1016/j.mad.2006.11.016
ContentType Journal Article
Copyright 2015 The Authors. published by the Anatomical Society and John Wiley & Sons Ltd.
2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
COPYRIGHT 2015 John Wiley & Sons, Inc.
Copyright © 2015 The Anatomical Society and John Wiley & Sons Ltd
2015 The Authors. published by the Anatomical Society and John Wiley & Sons Ltd. 2015
Copyright_xml – notice: 2015 The Authors. published by the Anatomical Society and John Wiley & Sons Ltd.
– notice: 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
– notice: COPYRIGHT 2015 John Wiley & Sons, Inc.
– notice: Copyright © 2015 The Anatomical Society and John Wiley & Sons Ltd
– notice: 2015 The Authors. published by the Anatomical Society and John Wiley & Sons Ltd. 2015
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Issue 3
Keywords pattern recognition receptors
peripheral blood mononuclear cells
immunosenescence
interferon signaling
innate immunity
innate immune agonists
Language English
License Attribution
http://creativecommons.org/licenses/by/4.0
2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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References 2010; 11
2009; 25
1993; 23
2014; 92
2007; 128
2000; 25
2004; 29
1984; 48
2010
1995; 57
2010; 125
2009
2002; 2
1970; 10
2008; 205
2004; 5
2008; 8
2011; 10
2005
2011; 12
2010; 184
2003; 19
2003; 51
2012; 11
2007a; 195
1996; 106
2013; 9
2000; 192
1994; 8
2012; 273
2009; 30
2013; 14
2009; 70
2013; 218
2013; 13
2005; 102
2002; 123
2007b; 178
2000; 121
2009; 4
2006; 127
2012; 24
2003; 124
2005; 17
2008; 82
2012; 44
2005; 79
e_1_2_9_31_1
e_1_2_9_50_1
e_1_2_9_10_1
e_1_2_9_35_1
e_1_2_9_12_1
e_1_2_9_33_1
e_1_2_9_14_1
e_1_2_9_39_1
e_1_2_9_16_1
e_1_2_9_37_1
e_1_2_9_18_1
Nikolich‐Zugich J (e_1_2_9_36_1) 2008; 8
e_1_2_9_41_1
e_1_2_9_20_1
e_1_2_9_45_1
e_1_2_9_24_1
e_1_2_9_43_1
e_1_2_9_8_1
e_1_2_9_6_1
e_1_2_9_4_1
e_1_2_9_26_1
e_1_2_9_49_1
e_1_2_9_28_1
e_1_2_9_47_1
e_1_2_9_30_1
e_1_2_9_11_1
e_1_2_9_13_1
Gon Y (e_1_2_9_22_1) 1996; 106
e_1_2_9_32_1
Molteni M (e_1_2_9_34_1) 1994; 8
e_1_2_9_15_1
e_1_2_9_38_1
e_1_2_9_17_1
e_1_2_9_19_1
e_1_2_9_40_1
R Core Team (e_1_2_9_42_1) 2010
Abb J (e_1_2_9_2_1) 1984; 48
e_1_2_9_21_1
e_1_2_9_46_1
e_1_2_9_23_1
e_1_2_9_44_1
e_1_2_9_7_1
e_1_2_9_5_1
e_1_2_9_3_1
e_1_2_9_9_1
e_1_2_9_25_1
e_1_2_9_27_1
e_1_2_9_48_1
e_1_2_9_29_1
23786540 - BMC Geriatr. 2013;13:64
12297345 - Mech Ageing Dev. 2002 Jul;123(10):1419-21
19541535 - Trends Immunol. 2009 Jul;30(7):325-33
17471428 - J Infect Dis. 2007 Jun 1;195(11):1590-7
24083425 - BMC Immunol. 2013;14:45
11164463 - Mech Ageing Dev. 2000 Dec 20;121(1-3):89-100
8870709 - Clin Exp Immunol. 1996 Oct;106(1):120-6
16516272 - Mech Ageing Dev. 2006 Jun;127(6):560-6
19596035 - Hum Immunol. 2009 Oct;70(10):777-84
22560929 - Semin Immunol. 2012 Oct;24(5):331-41
21074638 - Ageing Res Rev. 2011 Jul;10(3):346-53
23582781 - Immunobiology. 2013 Aug;218(8):1077-84
12932356 - Immunity. 2003 Aug;19(2):225-34
22564607 - Transplant Proc. 2012 May;44(4):996-8
12409046 - Lancet Infect Dis. 2002 Nov;2(11):659-66
19047440 - J Exp Med. 2008 Dec 22;205(13):3119-31
14511167 - J Am Geriatr Soc. 2003 Oct;51(10):1451-4
16227257 - J Virol. 2005 Nov;79(21):13350-61
12714244 - Mech Ageing Dev. 2003 Apr;124(4):389-93
16084711 - Curr Opin Immunol. 2005 Oct;17(5):457-62
17116321 - Mech Ageing Dev. 2007 Jan;128(1):92-105
21743478 - Nat Immunol. 2011 Aug;12(8):786-95
22708967 - Aging Cell. 2012 Oct;11(5):867-75
23633948 - PLoS Pathog. 2013;9(4):e1003298
19932918 - J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S53-72
24217812 - Immunol Cell Biol. 2014 Jan;92(1):72-9
15461798 - Genome Biol. 2004;5(10):R80
15181275 - Immunol Res. 2004;29(1-3):113-24
20565954 - BMC Immunol. 2010;11:30
11015443 - J Exp Med. 2000 Oct 2;192(7):1027-34
5420677 - Gerontologist. 1970 Spring;10(1):20-30
17202359 - J Immunol. 2007 Jan 15;178(2):970-5
22316526 - Cell Immunol. 2012;273(2):124-32
10802651 - Nat Genet. 2000 May;25(1):25-9
22023165 - Aging Cell. 2012 Feb;11(1):104-10
11164467 - Mech Ageing Dev. 2000 Dec 20;121(1-3):131-7
20100933 - J Immunol. 2010 Mar 1;184(5):2518-27
7863811 - J Biol Regul Homeost Agents. 1994 Apr-Jun;8(2):41-7
19033274 - Bioinformatics. 2009 Jan 15;25(2):288-9
6326901 - Blut. 1984 May;48(5):285-9
18469829 - Nat Rev Immunol. 2008 Jul;8(7):512-22
18508883 - J Virol. 2008 Aug;82(15):7613-23
8370415 - Eur J Immunol. 1993 Sep;23(9):2375-8
16199517 - Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
19131956 - Nat Protoc. 2009;4(1):44-57
References_xml – volume: 205
  start-page: 3119
  year: 2008
  end-page: 3131
  article-title: Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses
  publication-title: J. Exp. Med.
– volume: 8
  start-page: 41
  year: 1994
  end-page: 47
  article-title: Secretion of cytokines upon allogeneic stimulation: effect of aging
  publication-title: J. Biol. Regul. Homeost. Agents
– volume: 2
  start-page: 659
  year: 2002
  end-page: 666
  article-title: Ageing and infection
  publication-title: Lancet. Infect. Dis.
– year: 2009
– volume: 30
  start-page: 325
  year: 2009
  end-page: 333
  article-title: Human innate immunosenescence: causes and consequences for immunity in old age
  publication-title: Trends Immunol.
– volume: 17
  start-page: 457
  year: 2005
  end-page: 462
  article-title: The aging innate immune system
  publication-title: Curr. Opin. Immunol.
– volume: 123
  start-page: 1419
  year: 2002
  end-page: 1421
  article-title: CTLA‐4 upregulation during aging
  publication-title: Mech. Ageing Dev.
– volume: 192
  start-page: 1027
  year: 2000
  end-page: 1034
  article-title: Engagement of the PD‐1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation
  publication-title: J. Exp. Med.
– volume: 125
  start-page: S53
  year: 2010
  end-page: S72
  article-title: Immunologic messenger molecules: cytokines, interferons, and chemokines
  publication-title: J. Allergy Clin. Immunol.
– volume: 4
  start-page: 44
  year: 2009
  end-page: 57
  article-title: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
  publication-title: Nat. Protoc.
– volume: 10
  start-page: 20
  year: 1970
  end-page: 30
  article-title: Progress in development of the index of ADL
  publication-title: Gerontologist
– volume: 29
  start-page: 113
  year: 2004
  end-page: 124
  article-title: Immunity to influenza: the challenges of protecting an aging population
  publication-title: Immunol. Res.
– volume: 102
  start-page: 15545
  year: 2005
  end-page: 15550
  article-title: Gene set enrichment analysis: a knowledge‐based approach for interpreting genome‐wide expression profiles
  publication-title: Proc. Natl Acad. Sci. USA
– volume: 218
  start-page: 1077
  year: 2013
  end-page: 1084
  article-title: Ageing impairs the T cell response to dendritic cells
  publication-title: Immunobiology
– volume: 57
  start-page: 289
  year: 1995
  end-page: 300
  article-title: Controlling the false discovery rate: a practical and powerful approach to multiple testing
  publication-title: J. R. Stat. Soc. Series B Stat. Methodol.
– volume: 92
  start-page: 72
  year: 2014
  end-page: 79
  article-title: How T follicular helper cells and the germinal centre response change with age
  publication-title: Immunol. Cell Biol.
– volume: 273
  start-page: 124
  year: 2012
  end-page: 132
  article-title: Aging is associated with circulating cytokine dysregulation
  publication-title: Cell. Immunol.
– volume: 8
  start-page: 512
  year: 2008
  end-page: 522
  article-title: Ageing and life‐long maintenance of T‐cell subsets in the face of latent persistent infections. Nature reviews
  publication-title: Immunology
– volume: 184
  start-page: 2518
  year: 2010
  end-page: 2527
  article-title: Age‐associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response
  publication-title: J. Immunol.
– volume: 195
  start-page: 1590
  year: 2007a
  end-page: 1597
  article-title: Prevaccine determination of the expression of costimulatory B7 molecules in activated monocytes predicts influenza vaccine responses in young and older adults
  publication-title: J. Infect. Dis.
– volume: 51
  start-page: 1451
  year: 2003
  end-page: 1454
  article-title: The Mini‐Cog as a screen for dementia: validation in a population‐based sample
  publication-title: J. Am. Geriatr. Soc.
– volume: 48
  start-page: 285
  year: 1984
  end-page: 289
  article-title: Age‐related decline of human interferon alpha and interferon gamma production
  publication-title: Blut
– volume: 70
  start-page: 777
  year: 2009
  end-page: 784
  article-title: Aging is associated with a numerical and functional decline in plasmacytoid dendritic cells, whereas myeloid dendritic cells are relatively unaltered in human peripheral blood
  publication-title: Hum. Immunol.
– volume: 14
  start-page: 45
  year: 2013
  article-title: Age‐dependent changes in the expression of regulatory cell surface ligands in activated human T‐cells
  publication-title: BMC Immunol.
– volume: 10
  start-page: 346
  year: 2011
  end-page: 353
  article-title: Dysregulation of human Toll‐like receptor function in aging
  publication-title: Ageing Res. Rev.
– volume: 19
  start-page: 225
  year: 2003
  end-page: 234
  article-title: Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6
  publication-title: Immunity
– volume: 11
  start-page: 30
  year: 2010
  article-title: Age‐dependent alterations of monocyte subsets and monocyte‐related chemokine pathways in healthy adults
  publication-title: BMC Immunol.
– volume: 9
  start-page: e1003298
  year: 2013
  article-title: Systems analysis of a RIG‐I agonist inducing broad spectrum inhibition of virus infectivity
  publication-title: PLoS Pathog.
– volume: 25
  start-page: 25
  year: 2000
  end-page: 29
  article-title: Gene ontology: tool for the unification of biology. The Gene Ontology Consortium
  publication-title: Nat. Genet.
– volume: 11
  start-page: 867
  year: 2012
  end-page: 875
  article-title: Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function
  publication-title: Aging Cell
– volume: 12
  start-page: 786
  year: 2011
  end-page: 795
  article-title: Systems biology of vaccination for seasonal influenza in humans
  publication-title: Nat. Immunol.
– volume: 124
  start-page: 389
  year: 2003
  end-page: 393
  article-title: B cells in the aged: CD27, CD5, and CD40 expression
  publication-title: Mech. Ageing Dev.
– volume: 24
  start-page: 331
  year: 2012
  end-page: 341
  article-title: Innate immunosenescence: effect of aging on cells and receptors of the innate immune system in humans
  publication-title: Semin. Immunol.
– volume: 44
  start-page: 996
  year: 2012
  end-page: 998
  article-title: Monocyte‐derived CD40 expression is regulated by interferon‐gamma/interferon‐gamma receptor‐1 pathway when acting as a bridge during their interaction with T cells and allogeneic endothelial cells
  publication-title: Transpl. Proc.
– volume: 106
  start-page: 120
  year: 1996
  end-page: 126
  article-title: Lower serum concentrations of cytokines in elderly patients with pneumonia and the impaired production of cytokines by peripheral blood monocytes in the elderly
  publication-title: Clin. Exp. Immunol.
– volume: 5
  start-page: R80
  year: 2004
  article-title: Bioconductor: open software development for computational biology and bioinformatics
  publication-title: Genome Biol.
– volume: 121
  start-page: 89
  year: 2000
  end-page: 100
  article-title: Chemokine production by peripheral blood mononuclear cells in elderly subjects
  publication-title: Mech. Ageing Dev.
– year: 2010
– volume: 25
  start-page: 288
  year: 2009
  end-page: 289
  article-title: AmiGO: online access to ontology and annotation data
  publication-title: Bioinformatics
– volume: 128
  start-page: 92
  year: 2007
  end-page: 105
  article-title: Inflammaging and anti‐inflammaging: a systemic perspective on aging and longevity emerged from studies in humans
  publication-title: Mech. Ageing Dev.
– volume: 23
  start-page: 2375
  year: 1993
  end-page: 2378
  article-title: Increased cytokine production in mononuclear cells of healthy elderly people
  publication-title: Eur. J. Immunol.
– start-page: 397
  year: 2005
  end-page: 420
– volume: 178
  start-page: 970
  year: 2007b
  end-page: 975
  article-title: Age‐associated defect in human TLR‐1/2 function
  publication-title: J. Immunol.
– volume: 13
  start-page: 64
  year: 2013
  article-title: Measures of frailty in population‐based studies: an overview
  publication-title: BMC Geriatr.
– volume: 11
  start-page: 104
  year: 2012
  end-page: 110
  article-title: Age‐associated elevation in TLR5 leads to increased inflammatory responses in the elderly
  publication-title: Aging Cell
– volume: 79
  start-page: 13350
  year: 2005
  end-page: 13361
  article-title: Alpha/beta interferon protects against lethal West Nile virus infection by restricting cellular tropism and enhancing neuronal survival
  publication-title: J. Virol.
– volume: 82
  start-page: 7613
  year: 2008
  end-page: 7623
  article-title: Dysregulation of TLR3 impairs the innate immune response to West Nile virus in the elderly
  publication-title: J. Virol.
– volume: 121
  start-page: 131
  year: 2000
  end-page: 137
  article-title: Reduced IFN‐gamma production in elderly people following in vitro stimulation with influenza vaccine and endotoxin
  publication-title: Mech. Ageing Dev.
– volume: 127
  start-page: 560
  year: 2006
  end-page: 566
  article-title: Age‐dependent modifications of Type 1 and Type 2 cytokines within virgin and memory CD4+ T cells in humans
  publication-title: Mech. Ageing Dev.
– ident: e_1_2_9_44_1
  doi: 10.1186/1471-2172-11-30
– ident: e_1_2_9_13_1
  doi: 10.1086/516788
– ident: e_1_2_9_12_1
  doi: 10.1016/j.jaci.2009.07.008
– ident: e_1_2_9_27_1
  doi: 10.1016/j.humimm.2009.07.005
– ident: e_1_2_9_28_1
  doi: 10.1093/geront/10.1_Part_1.20
– ident: e_1_2_9_24_1
  doi: 10.1111/j.1474-9726.2012.00851.x
– ident: e_1_2_9_10_1
  doi: 10.1093/bioinformatics/btn615
– ident: e_1_2_9_37_1
  doi: 10.1016/S0047-6374(00)00204-9
– ident: e_1_2_9_4_1
  doi: 10.1016/j.cellimm.2012.01.001
– ident: e_1_2_9_29_1
  doi: 10.1385/IR:29:1-3:113
– ident: e_1_2_9_6_1
  doi: 10.1111/j.2517-6161.1995.tb02031.x
– ident: e_1_2_9_15_1
  doi: 10.1002/eji.1830230950
– ident: e_1_2_9_17_1
  doi: 10.1084/jem.192.7.1027
– ident: e_1_2_9_3_1
  doi: 10.1016/j.mad.2006.01.014
– ident: e_1_2_9_18_1
  doi: 10.1084/jem.20082292
– ident: e_1_2_9_45_1
  doi: 10.1016/j.arr.2010.10.007
– ident: e_1_2_9_33_1
  doi: 10.1038/icb.2013.77
– ident: e_1_2_9_26_1
  doi: 10.1016/S1074-7613(03)00208-5
– ident: e_1_2_9_21_1
  doi: 10.1016/j.coi.2005.07.013
– ident: e_1_2_9_11_1
  doi: 10.1016/S0047-6374(03)00013-7
– ident: e_1_2_9_31_1
  doi: 10.1128/JVI.00618-08
– ident: e_1_2_9_47_1
  doi: 10.1016/j.smim.2012.04.008
– ident: e_1_2_9_14_1
  doi: 10.4049/jimmunol.178.2.970
– ident: e_1_2_9_30_1
– ident: e_1_2_9_39_1
  doi: 10.4049/jimmunol.0901022
– ident: e_1_2_9_32_1
  doi: 10.1016/S0047-6374(02)00077-5
– volume: 48
  start-page: 285
  year: 1984
  ident: e_1_2_9_2_1
  article-title: Age‐related decline of human interferon alpha and interferon gamma production
  publication-title: Blut
  doi: 10.1007/BF00320399
– ident: e_1_2_9_46_1
  doi: 10.1007/0-387-29362-0_23
– ident: e_1_2_9_7_1
  doi: 10.1046/j.1532-5415.2003.51465.x
– ident: e_1_2_9_41_1
  doi: 10.1111/j.1474-9726.2011.00759.x
– ident: e_1_2_9_40_1
  doi: 10.1016/S0047-6374(00)00200-1
– ident: e_1_2_9_5_1
  doi: 10.1038/75556
– ident: e_1_2_9_19_1
  doi: 10.1016/S1473-3099(02)00437-1
– ident: e_1_2_9_9_1
  doi: 10.1186/1471-2172-14-45
– volume: 8
  start-page: 41
  year: 1994
  ident: e_1_2_9_34_1
  article-title: Secretion of cytokines upon allogeneic stimulation: effect of aging
  publication-title: J. Biol. Regul. Homeost. Agents
– ident: e_1_2_9_25_1
  doi: 10.1038/nprot.2008.211
– ident: e_1_2_9_38_1
  doi: 10.1016/j.it.2009.05.004
– ident: e_1_2_9_23_1
  doi: 10.1371/journal.ppat.1003298
– ident: e_1_2_9_20_1
  doi: 10.1186/gb-2004-5-10-r80
– volume: 106
  start-page: 120
  year: 1996
  ident: e_1_2_9_22_1
  article-title: Lower serum concentrations of cytokines in elderly patients with pneumonia and the impaired production of cytokines by peripheral blood monocytes in the elderly
  publication-title: Clin. Exp. Immunol.
– ident: e_1_2_9_35_1
  doi: 10.1038/ni.2067
– volume: 8
  start-page: 512
  year: 2008
  ident: e_1_2_9_36_1
  article-title: Ageing and life‐long maintenance of T‐cell subsets in the face of latent persistent infections. Nature reviews
  publication-title: Immunology
– ident: e_1_2_9_50_1
  doi: 10.1016/j.transproceed.2012.01.096
– ident: e_1_2_9_43_1
  doi: 10.1128/JVI.79.21.13350-13361.2005
– ident: e_1_2_9_8_1
  doi: 10.1186/1471-2318-13-64
– ident: e_1_2_9_49_1
  doi: 10.1016/j.imbio.2013.02.002
– ident: e_1_2_9_48_1
  doi: 10.1073/pnas.0506580102
– ident: e_1_2_9_16_1
  doi: 10.1016/j.mad.2006.11.016
– volume-title: R: A Language and Environment for Statistical computing
  year: 2010
  ident: e_1_2_9_42_1
– reference: 22560929 - Semin Immunol. 2012 Oct;24(5):331-41
– reference: 15461798 - Genome Biol. 2004;5(10):R80
– reference: 11164463 - Mech Ageing Dev. 2000 Dec 20;121(1-3):89-100
– reference: 19033274 - Bioinformatics. 2009 Jan 15;25(2):288-9
– reference: 21743478 - Nat Immunol. 2011 Aug;12(8):786-95
– reference: 12409046 - Lancet Infect Dis. 2002 Nov;2(11):659-66
– reference: 19131956 - Nat Protoc. 2009;4(1):44-57
– reference: 22564607 - Transplant Proc. 2012 May;44(4):996-8
– reference: 7863811 - J Biol Regul Homeost Agents. 1994 Apr-Jun;8(2):41-7
– reference: 22316526 - Cell Immunol. 2012;273(2):124-32
– reference: 16084711 - Curr Opin Immunol. 2005 Oct;17(5):457-62
– reference: 17471428 - J Infect Dis. 2007 Jun 1;195(11):1590-7
– reference: 12297345 - Mech Ageing Dev. 2002 Jul;123(10):1419-21
– reference: 11015443 - J Exp Med. 2000 Oct 2;192(7):1027-34
– reference: 18469829 - Nat Rev Immunol. 2008 Jul;8(7):512-22
– reference: 19541535 - Trends Immunol. 2009 Jul;30(7):325-33
– reference: 23786540 - BMC Geriatr. 2013;13:64
– reference: 23633948 - PLoS Pathog. 2013;9(4):e1003298
– reference: 24083425 - BMC Immunol. 2013;14:45
– reference: 17202359 - J Immunol. 2007 Jan 15;178(2):970-5
– reference: 16516272 - Mech Ageing Dev. 2006 Jun;127(6):560-6
– reference: 21074638 - Ageing Res Rev. 2011 Jul;10(3):346-53
– reference: 5420677 - Gerontologist. 1970 Spring;10(1):20-30
– reference: 17116321 - Mech Ageing Dev. 2007 Jan;128(1):92-105
– reference: 19932918 - J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S53-72
– reference: 10802651 - Nat Genet. 2000 May;25(1):25-9
– reference: 23582781 - Immunobiology. 2013 Aug;218(8):1077-84
– reference: 22023165 - Aging Cell. 2012 Feb;11(1):104-10
– reference: 11164467 - Mech Ageing Dev. 2000 Dec 20;121(1-3):131-7
– reference: 12932356 - Immunity. 2003 Aug;19(2):225-34
– reference: 6326901 - Blut. 1984 May;48(5):285-9
– reference: 16227257 - J Virol. 2005 Nov;79(21):13350-61
– reference: 8870709 - Clin Exp Immunol. 1996 Oct;106(1):120-6
– reference: 8370415 - Eur J Immunol. 1993 Sep;23(9):2375-8
– reference: 18508883 - J Virol. 2008 Aug;82(15):7613-23
– reference: 14511167 - J Am Geriatr Soc. 2003 Oct;51(10):1451-4
– reference: 12714244 - Mech Ageing Dev. 2003 Apr;124(4):389-93
– reference: 22708967 - Aging Cell. 2012 Oct;11(5):867-75
– reference: 19596035 - Hum Immunol. 2009 Oct;70(10):777-84
– reference: 20565954 - BMC Immunol. 2010;11:30
– reference: 16199517 - Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
– reference: 24217812 - Immunol Cell Biol. 2014 Jan;92(1):72-9
– reference: 19047440 - J Exp Med. 2008 Dec 22;205(13):3119-31
– reference: 15181275 - Immunol Res. 2004;29(1-3):113-24
– reference: 20100933 - J Immunol. 2010 Mar 1;184(5):2518-27
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Snippet Summary Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to...
Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines...
Summary Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to...
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StartPage 421
SubjectTerms Adaptive Immunity - genetics
Adult
Aged
Aged, 80 and over
Aging
B cells
B-Lymphocytes - immunology
Biological response modifiers
Chemokines - metabolism
Comparative analysis
Cytokines - metabolism
Dendritic cells
Dendritic Cells - immunology
Disease susceptibility
Health aspects
Humans
Immune response
Immune system
Immunity, Innate - immunology
immunosenescence
Immunotherapy
innate immune agonists
innate immunity
Interferon
interferon signaling
Leukocytes, Mononuclear - metabolism
Lymphocyte Activation - genetics
Lymphocytes
Monocytes - immunology
Original
pattern recognition receptors
peripheral blood mononuclear cells
T cells
T-Lymphocytes - immunology
Vaccines
Young Adult
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Title Global analyses revealed age‐related alterations in innate immune responses after stimulation of pathogen recognition receptors
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