Aging of the Innate Immune System: An Update - PubMed (original) (raw)
Aging of the Innate Immune System: An Update
Shegufta Mahbub et al. Curr Immunol Rev. 2011.
Abstract
The relationship between advanced age and immunologic deficits is becoming an area of rapidly advancing research. Many of the clinical hurdles in the elderly population result from dysregulation of the immune system leading to the inability of the elderly to swiftly combat infection and to the increased incidence of chronic disease states and autoimmune conditions. Herein, we address the crucial alterations in the innate immune system that occur with advancing age. Specifically, we discuss how the effects of advanced age may lead to functional changes in the neutrophil, macrophage, dendritic cell, natural killer cell, and natural killer T cell populations in human and murine models that translate into aberrant innate immune responses. Furthermore, we elucidate how these changes may contribute to documented deficits in adaptive immunity as well as the pathological conditions and the increased morbidity and mortality seen in the elderly population.
Figures
Fig. (1)
Neutrophil defects with advanced age. Arrows (↑, ↓ or ↔) denote increased, decreased or unaltered levels in the aged compared to the young. Abbreviations: fMLP, N-formyl-methionyl-leucyl-phenylalanine; GM-CSF, granulocyte monocyte colony stimulating factor; LPS, lipopolysaccharide; TREM-1, triggering receptor expressed on myeloid cell-1, TLR4, Toll-like receptor 4; MyD88, Myeloid differentiation primary response gene (88); IP3, inositol 1,4,5-triphosphate; DAG, diacyl glycerol; cAMP/PKA, cyclic adenosine monophosphate/protein kinase A; ERK, extracellular signal-regulated protein kinase; MAPK, mitogen activated protein kinase; SHP-1, inhibitor of Src family of tyrosine kinases, SOCs, suppressors of cytokine signaling.
Fig. (2)
Macrophage defects with advanced a ge. Arrows (↑, ↓ or ↔) denote increased, decreased or unaltered levels in the aged compared to the young. Abbreviations: IFN-γ, interferon-gamma; ROS, reactive oxygen species; MHC, major histocompatibility complex; RNS, reactive nitrogen species; iNOS, inducible nitric oxide synthase; LBP, LPS-binding protein; JNK, janus kinase; MAPK, mitogen activated protein kinase; PGE2, prostaglandin E2; I-κB, inhibitor of κB; NF-κB, nuclear factor-kappaB; COX, cyclooxygenase; TNF-α, tumor necrosis factor-alpha; MIP, macrophage inflammatory protein; IL, interleukin.
Fig. (3)
Dendritic cell defects with advanced age. Arrows (↑, ↓ or ↔) denote increased, decreased or unaltered levels in the aged compared to the young. Abbreviations: mDC, myleiod dendritic cell; MDDC, monocyte-derived dendritic cell; pDC, plasmacytoid dendritic cell; LC, Langerhan’s cell; LPS, lipopolysaccharide; PI3K, Phosphoinositide-3 kinase; AKT, serine/threonine kinase; MIP, macrophage inflammatory protein; TNF-α, tumor necrosis factor-alpha; IL, interleukin; ssRNA, single-stranded ribonucleic acid; IFN-γ, interferon-gamma; IRF, interferon regulation factor; HSV, herpes simplex virus.
Similar articles
- Age-related Dysregulation of Inflammation and Innate Immunity: Lessons Learned from Rodent Models.
Brubaker AL, Palmer JL, Kovacs EJ. Brubaker AL, et al. Aging Dis. 2011 Oct;2(5):346-60. Epub 2011 Oct 28. Aging Dis. 2011. PMID: 22396887 Free PMC article. - Impaired immune responses in the lungs of aged mice following influenza infection.
Toapanta FR, Ross TM. Toapanta FR, et al. Respir Res. 2009 Nov 18;10(1):112. doi: 10.1186/1465-9921-10-112. Respir Res. 2009. PMID: 19922665 Free PMC article. - Neutrophil ageing and immunesenescence.
Lord JM, Butcher S, Killampali V, Lascelles D, Salmon M. Lord JM, et al. Mech Ageing Dev. 2001 Sep 30;122(14):1521-35. doi: 10.1016/s0047-6374(01)00285-8. Mech Ageing Dev. 2001. PMID: 11511394 Review. - Senescent remodeling of the immune system and its contribution to the predisposition of the elderly to infections.
Dewan SK, Zheng SB, Xia SJ, Bill K. Dewan SK, et al. Chin Med J (Engl). 2012 Sep;125(18):3325-31. Chin Med J (Engl). 2012. PMID: 22964331 Review. - T cell senescence.
Linton P, Thoman ML. Linton P, et al. Front Biosci. 2001 Feb 1;6:D248-61. doi: 10.2741/linton. Front Biosci. 2001. PMID: 11171551 Review.
Cited by
- Modeling the CD8+ T cell immune response to influenza infection in adult and aged mice.
Whipple B, Miura TA, Hernandez-Vargas EA. Whipple B, et al. J Theor Biol. 2024 Oct 7;593:111898. doi: 10.1016/j.jtbi.2024.111898. Epub 2024 Jul 10. J Theor Biol. 2024. PMID: 38996911 - Age-dependent ventilator-induced lung injury: Mathematical modeling, experimental data, and statistical analysis.
Hay Q, Grubb C, Minucci S, Valentine MS, Van Mullekom J, Heise RL, Reynolds AM. Hay Q, et al. PLoS Comput Biol. 2024 Feb 22;20(2):e1011113. doi: 10.1371/journal.pcbi.1011113. eCollection 2024 Feb. PLoS Comput Biol. 2024. PMID: 38386693 Free PMC article. - Geriatric Surgery Produces a Hypoactive Molecular Phenotype in the Monocyte Immune Gene Transcriptome.
Oren RL, Grasfield RH, Friese MB, Chibnik LB, Chi JH, Groff MW, Kang JD, Xie Z, Culley DJ, Crosby G. Oren RL, et al. J Clin Med. 2023 Sep 28;12(19):6271. doi: 10.3390/jcm12196271. J Clin Med. 2023. PMID: 37834915 Free PMC article. - Hypoxic State of Cells and Immunosenescence: A Focus on the Role of the HIF Signaling Pathway.
Troise D, Infante B, Mercuri S, Netti GS, Ranieri E, Gesualdo L, Stallone G, Pontrelli P. Troise D, et al. Biomedicines. 2023 Aug 1;11(8):2163. doi: 10.3390/biomedicines11082163. Biomedicines. 2023. PMID: 37626660 Free PMC article. Review. - Endoplasmic Reticulum Stress in Elderly Patients with COVID-19: Potential of Melatonin Treatment.
Yiang GT, Wu CC, Lu CL, Hu WC, Tsai YJ, Huang YM, Su WL, Lu KC. Yiang GT, et al. Viruses. 2023 Jan 4;15(1):156. doi: 10.3390/v15010156. Viruses. 2023. PMID: 36680196 Free PMC article. Review.
References
- Vu T, Farish S, Jenkins M, Kelly H. A meta-analysis of effectiveness of influenza vaccine in persons aged 65 years and over living in the community. Vaccine. 2002;20(13–14):1831–1836. - PubMed
- Franceschi C, Bonafe M, Valensin S, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–254. - PubMed
- Lowell CA, Berton G. Integrin signal transduction in myeloid leukocytes. J Leukoc Biol. 1999;65(3):313–320. - PubMed
Grants and funding
- R01 AG018859-08/AG/NIA NIH HHS/United States
- T32 AG031780/AG/NIA NIH HHS/United States
- T32 AG031780-02/AG/NIA NIH HHS/United States
- R01 AI056108-05/AI/NIAID NIH HHS/United States
- R01 AG018859-07/AG/NIA NIH HHS/United States
- R01 AG018859-10/AG/NIA NIH HHS/United States
- R01 AG018859-09/AG/NIA NIH HHS/United States
- R01 AI056108/AI/NIAID NIH HHS/United States
- R01 AG018859/AG/NIA NIH HHS/United States
LinkOut - more resources
Full Text Sources