Skip to main content
SpringerLink
Log in

Natural Killer Cells and Health Status: Age, CMV Infection, and Obesity

Handbook of Immunosenescence

  • 217 Accesses

Abstract

In human, not only ageing but also chronic stimulation of the immune system (such as viral infections), inflammation, and alterations in nutrition can affect NK cells provoking changes in their receptors expression, cytotoxicity, and response to cytokines. In these clinical circumstances frequently associated with ageing, NK cell functional capacity can be diminished, contributing to immunosenescence, which will render in higher incidence of morbidity and mortality in aged individuals. Therefore, in healthy elderly, including centenarians, NK cell number and function are well preserved, while an increased incidence of infectious and inflammatory diseases and increased risk of death due to infection in the elderly is associated with a decrease in NK cell activity. Furthermore, there is evidence that NK cell function is affected in obese individuals, and it is associated with an increased risk of cancer. The chronic state of inflammation in obesity might contribute to T and NK cell immunosenescence and cytomegalovirus (CMV) reactivation. Here, we describe recent data regarding the effects of ageing, CMV infection, nutrition, and inflammation on NK cells and its consequences on health status.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Similar content being viewed by others

References

  • Alam I, Larbi A, Pawelec G (2012) Nutritional status influences peripheral immune cell phenotypes in healthy men in rural Pakistan. Immun Ageing 9:16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ali TH, Pisanti S, Ciaglia E, Mortarini R, Anichini A, Garofalo C, Tallerico R, Santinami M, Gulletta E, Ietto C, Galgani M, Matarese G, Bifulco M, Ferrone S, Colucci F, Moretta A, Karre K, Carbone E (2014) Enrichment of CD56(dim)KIR + CD57 + highly cytotoxic NK cells in tumour-infiltrated lymph nodes of melanoma patients. Nat Commun 5:5639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alonso-Fernandez P, De La Fuente M (2011) Role of the immune system in aging and longevity. Curr Aging Sci 4:78–100

    Article  CAS  PubMed  Google Scholar 

  • Apostolopoulos V, De Courten MP, Stojanovska L, Blatch GL, Tangalakis K, De Courten B (2016) The complex immunological and inflammatory network of adipose tissue in obesity. Mol Nutr Food Res 60:43–57

    Article  CAS  PubMed  Google Scholar 

  • Arreola R, Quintero-Fabian S, Lopez-Roa RI, Flores-Gutierrez EO, Reyes-Grajeda JP, Carrera-Quintanar L, Ortuno-Sahagun D (2015) Immunomodulation and anti-inflammatory effects of garlic compounds. J Immunol Res 2015:401630

    PubMed  PubMed Central  Google Scholar 

  • Aviv A, Valdes A, Gardner JP, Swaminathan R, Kimura M, Spector TD (2006) Menopause modifies the association of leukocyte telomere length with insulin resistance and inflammation. J Clin Endocrinol Metab 91:635–640

    Article  CAS  PubMed  Google Scholar 

  • Balch CM, Tilden AB, Dougherty PA, Cloud GA (1983) Depressed levels of granular lymphocytes with natural killer (NK) cell function in 247 cancer patients. Ann Surg 198:192–199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ballesteros-Pomar MD, Calleja S, Diez-Rodriguez R, Calleja-Fernandez A, Vidal-Casariego A, Nunez-Alonso A, Cano-Rodriguez I, Olcoz-Goni JL (2014) Inflammatory status is different in relationship to insulin resistance in severely obese people and changes after bariatric surgery or diet-induced weight loss. Exp Clin Endocrinol Diabetes 122:592–596

    Article  CAS  PubMed  Google Scholar 

  • Barra NG, Chew MV, Holloway AC, Ashkar AA (2012) Interleukin-15 treatment improves glucose homeostasis and insulin sensitivity in obese mice. Diabetes Obes Metab 14:190–193

    Article  CAS  PubMed  Google Scholar 

  • Bartlett DB, Firth CM, Phillips AC, Moss P, Baylis D, Syddall H, Sayer AA, Cooper C, Lord JM (2012) The age-related increase in low-grade systemic inflammation (Inflammaging) is not driven by cytomegalovirus infection. Aging Cell 11:912–915

    Article  CAS  PubMed  Google Scholar 

  • Batista MD, Ho EL, Kuebler PJ, Milush JM, Lanier LL, Kallas EG, York VA, Chang D, Liao W, Unemori P, Leslie KS, Maurer T, Nixon DF (2013) Skewed distribution of natural killer cells in psoriasis skin lesions. Exp Dermatol 22:64–66

    Article  PubMed  PubMed Central  Google Scholar 

  • Beziat V, Liu LL, Malmberg JA, Ivarsson MA, Sohlberg E, Bjorklund AT, Retiere C, Sverremark-Ekstrom E, Traherne J, Ljungman P, Schaffer M, Price DA, Trowsdale J, Michaelsson J, Ljunggren HG, Malmberg KJ (2013) NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRs. Blood 121:2678–2688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bigley AB, Rezvani K, Shah N, Sekine T, Balneger N, Pistillo M, Agha N, Kunz H, Bollard CM, O’Connor DP, Simpson RJ (2016) Latent CMV infection enhances anti-tumor cytotoxicity through accumulation of NKG2C+ NK-cells in healthy humans. Clin Exp Immunol 185:239–251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boynton A, Neuhouser ML, Wener MH, Wood B, Sorensen B, Chen-Levy Z, Kirk EA, Yasui Y, Lacroix K, Mctiernan A, Ulrich CM (2007) Associations between healthy eating patterns and immune function or inflammation in overweight or obese postmenopausal women. Am J Clin Nutr 86:1445–1455

    CAS  PubMed  Google Scholar 

  • Bruunsgaard H, Pedersen AN, Schroll M, Skinhoj P, Pedersen BK (2001) Decreased natural killer cell activity is associated with atherosclerosis in elderly humans. Exp Gerontol 37:127–136

    Article  CAS  PubMed  Google Scholar 

  • Camous X, Pera A, Solana R, Larbi A (2012) NK cells in healthy aging and age-associated diseases. J Biomed Biotechnol 2012:195956

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Campos C, Pera A, Lopez-Fernandez I, Alonso C, Tarazona R, Solana R (2014a) Proinflammatory status influences NK cells subsets in the elderly. Immunol Lett 162:298–302

    Article  CAS  PubMed  Google Scholar 

  • Campos C, Pera A, Sanchez-Correa B, Alonso C, Lopez-Fernandez I, Morgado S, Tarazona R, Solana R (2014b) Effect of age and CMV on NK cell subpopulations. Exp Gerontol 54:130–137

    Article  CAS  PubMed  Google Scholar 

  • Campos C, Lopez N, Pera A, Gordillo JJ, Hassouneh F, Tarazona R, Solana R (2015) Expression of NKp30, NKp46 and DNAM-1 activating receptors on resting and IL-2 activated NK cells from healthy donors according to CMV-serostatus and age. Biogerontology 16:671–683

    Article  CAS  PubMed  Google Scholar 

  • Carrega P, Ferlazzo G (2012) Natural killer cell distribution and trafficking in human tissues. Front Immunol 3:347

    Article  PubMed  PubMed Central  Google Scholar 

  • Chandra RK (1980) Cell-mediated immunity in genetically obese (C57BL/6J ob/ob) mice. Am J Clin Nutr 33:13–16

    CAS  PubMed  Google Scholar 

  • Costa-Garcia M, Vera A, Moraru M, Vilches C, Lopez-Botet M, Muntasell A (2015) Antibody-mediated response of NKG2Cbright NK cells against human cytomegalovirus. J Immunol 194:2715–2724

    Article  CAS  PubMed  Google Scholar 

  • Dalbeth N, Callan MF (2002) A subset of natural killer cells is greatly expanded within inflamed joints. Arthritis Rheum 46:1763–1772

    Article  PubMed  Google Scholar 

  • Delarosa O, Pawelec G, Peralbo E, Wikby A, Mariani E, Mocchegiani E, Tarazona R, Solana R (2006) Immunological biomarkers of ageing in man: changes in both innate and adaptive immunity are associated with health and longevity. Biogerontology 7:471–481

    Article  CAS  PubMed  Google Scholar 

  • Djaoud Z, Riou R, Gavlovsky PJ, Mehlal S, Bressollette C, Gerard N, Gagne K, Charreau B, Retiere C (2016) Cytomegalovirus-infected primary endothelial cells trigger NKG2C+ natural killer cells. J Innate Immun 8:374–385

    Article  CAS  PubMed  Google Scholar 

  • Dotta F, Censini S, Van Halteren AG, Marselli L, Masini M, Dionisi S, Mosca F, Boggi U, Muda AO, Del Prato S, Elliott JF, Covacci A, Rappuoli R, Roep BO, Marchetti P (2007) Coxsackie B4 virus infection of beta cells and natural killer cell insulitis in recent-onset type 1 diabetic patients. Proc Natl Acad Sci U S A 104:5115–5120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dovio A, Caramello V, Masera RG, Sartori ML, Saba L, Tinivella M, Prolo P, Termine A, Avagnina P, Angeli A (2004) Natural killer cell activity and sensitivity to positive and negative modulation in uncomplicated obese subjects: relationships to leptin and diet composition. Int J Obes Relat Metab Disord 28:894–901

    Article  CAS  PubMed  Google Scholar 

  • Dowd JB, Aiello AE (2009) Socioeconomic differentials in immune response. Epidemiology 20:902–908

    Article  PubMed  PubMed Central  Google Scholar 

  • Fantuzzi G, Faggioni R (2000) Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol 68:437–446

    CAS  PubMed  Google Scholar 

  • Fernandez-Riejos P, Najib S, Santos-Alvarez J, Martin-Romero C, Perez-Perez A, Gonzalez-Yanes C, Sanchez-Margalet V (2010) Role of leptin in the activation of immune cells. Mediat Inflamm 2010:568343

    Article  CAS  Google Scholar 

  • Ferrando-Martinez S, De La Fuente M, Guerrero JM, Leal M, Munoz-Fernandez MA (2013a) Impact of thymic function in age-related immune deterioration. Rev Esp Geriatr Gerontol 48:232–237

    Article  PubMed  Google Scholar 

  • Ferrando-Martinez S, Romero-Sanchez MC, Solana R, Delgado J, De La Rosa R, Munoz-Fernandez MA, Ruiz-Mateos E, Leal M (2013b) Thymic function failure and C-reactive protein levels are independent predictors of all-cause mortality in healthy elderly humans. Age (Dordr) 35:251–259

    Article  CAS  Google Scholar 

  • Ferson M, Edwards A, Lind A, Milton GW, Hersey P (1979) Low natural killer-cell activity and immunoglobulin levels associated with smoking in human subjects. Int J Cancer 23:603–609

    Article  CAS  PubMed  Google Scholar 

  • Formiga F, Ferrer A, Padros G, Cintra A, Pujol R (2014) Inverted CD4:CD8 ratio is not associated with three-year mortality in a sample of community-dwelling oldest old: the OCTABAIX immune study. J Nutr Health Aging 18:425–428

    Article  CAS  PubMed  Google Scholar 

  • Franceschi C, Monti D, Sansoni P, Cossarizza A (1995) The immunology of exceptional individuals: the lesson of centenarians. Immunol Today 16:12–16

    Article  CAS  PubMed  Google Scholar 

  • Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254

    Article  CAS  PubMed  Google Scholar 

  • Gameiro CM, Romao F, Castelo-Branco C (2010) Menopause and aging: changes in the immune system – a review. Maturitas 67:316–320

    Article  CAS  PubMed  Google Scholar 

  • Grossmann ME, Ray A, Nkhata KJ, Malakhov DA, Rogozina OP, Dogan S, Cleary MP (2010) Obesity and breast cancer: status of leptin and adiponectin in pathological processes. Cancer Metastasis Rev 29:641–653

    Article  CAS  PubMed  Google Scholar 

  • Guma M, Budt M, Saez A, Brckalo T, Hengel H, Angulo A, Lopez-Botet M (2006) Expansion of CD94/NKG2C+ NK cells in response to human cytomegalovirus-infected fibroblasts. Blood 107:3624–3631

    Article  CAS  PubMed  Google Scholar 

  • Guo H, Xu B, Gao L, Sun X, Qu X, Li X, Liu S, Feng J, Wang J, Tang Y, Yan G, Gao X, Jiang Y (2012) High frequency of activated natural killer and natural killer T-cells in patients with new onset of type 2 diabetes mellitus. Exp Biol Med (Maywood) 237:556–562

    Article  CAS  Google Scholar 

  • Halenius A, Hengel H (2014) Human cytomegalovirus and autoimmune disease. Biomed Res Int 2014:472978

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jahn J, Spielau M, Brandsch C, Stangl GI, Delank KS, Bahr I, Berreis T, Wrann CD, Kielstein H (2015) Decreased NK cell functions in obesity can be reactivated by fat mass reduction. Obesity (Silver Spring) 23:2233–2241

    Article  CAS  Google Scholar 

  • Jarde T, Perrier S, Vasson MP, Caldefie-Chezet F (2011) Molecular mechanisms of leptin and adiponectin in breast cancer. Eur J Cancer 47:33–43

    Article  CAS  PubMed  Google Scholar 

  • Kanda T, Takahashi T, Kudo S, Takeda T, Tsugawa H, Takekoshi N (2004) Leptin deficiency enhances myocardial necrosis and lethality in a murine model of viral myocarditis. Life Sci 75:1435–1447

    Article  CAS  PubMed  Google Scholar 

  • Kang YE, Kim JM, Joung KH, Lee JH, You BR, Choi MJ, Ryu MJ, Ko YB, Lee MA, Lee J, Ku BJ, Shong M, Lee KH, Kim HJ (2016) The roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in obesity-associated insulin resistance in modest obesity and early metabolic dysfunction. PLoS One 11:e0154003

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lamas B, Goncalves-Mendes N, Nachat-Kappes R, Rossary A, Caldefie-Chezet F, Vasson MP, Farges MC (2013) Leptin modulates dose-dependently the metabolic and cytolytic activities of NK-92 cells. J Cell Physiol 228:1202–1209

    Article  CAS  PubMed  Google Scholar 

  • Lamas B, Nachat-Kappes R, Goncalves-Mendes N, Mishellany F, Rossary A, Vasson MP, Farges MC (2015) Dietary fat without body weight gain increases in vivo MCF-7 human breast cancer cell growth and decreases natural killer cell cytotoxicity. Mol Carcinog 54:58–71

    Article  CAS  PubMed  Google Scholar 

  • Larbi A, Franceschi C, Mazzatti D, Solana R, Wikby A, Pawelec G (2008) Aging of the immune system as a prognostic factor for human longevity. Physiology (Bethesda) 23:64–74

    Article  CAS  Google Scholar 

  • Laue T, Wrann CD, Hoffmann-Castendiek B, Pietsch D, Hubner L, Kielstein H (2015) Altered NK cell function in obese healthy humans. BMC Obes 2:1

    Article  PubMed  PubMed Central  Google Scholar 

  • Lautenbach A, Breitmeier D, Kuhlmann S, Nave H (2011) Human obesity reduces the number of hepatic leptin receptor (ob-R) expressing NK cells. Endocr Res 36:158–166

    Article  CAS  PubMed  Google Scholar 

  • Le Garff-Tavernier M, Beziat V, Decocq J, Siguret V, Gandjbakhch F, Pautas E, Debre P, Merle-Beral H, Vieillard V (2010) Human NK cells display major phenotypic and functional changes over the life span. Aging Cell 9:527–535

    Article  CAS  PubMed  Google Scholar 

  • Lee J, Zhang T, Hwang I, Kim A, Nitschke L, Kim M, Scott JM, Kamimura Y, Lanier LL, Kim S (2015) Epigenetic modification and antibody-dependent expansion of memory-like NK cells in human cytomegalovirus-infected individuals. Immunity 42:431–442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee BC, Kim MS, Pae M, Yamamoto Y, Eberle D, Shimada T, Kamei N, Park HS, Sasorith S, Woo JR, You J, Mosher W, Brady HJ, Shoelson SE, Lee J (2016) Adipose natural killer cells regulate adipose tissue macrophages to promote insulin resistance in obesity. Cell Metab 23:685–698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levy SM, Herberman RB, Lee J, Whiteside T, Beadle M, Heiden L, Simons A (1991) Persistently low natural killer cell activity, age, and environmental stress as predictors of infectious morbidity. Nat Immun Cell Growth Regul 10:289–307

    CAS  PubMed  Google Scholar 

  • Liu Y, Mu R, Gao YP, Dong J, Zhu L, Ma Y, Li YH, Zhang HQ, Han D, Zhang Y, Mcinnes IB, Zhang J, Shen B, Yang G, Li ZG (2016) A cytomegalovirus peptide-specific antibody alters natural killer cell homeostasis and is shared in several autoimmune diseases. Cell Host Microbe 19:400–408

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Verges S, Milush JM, Schwartz BS, Pando MJ, Jarjoura J, York VA, Houchins JP, Miller S, Kang SM, Norris PJ, Nixon DF, Lanier LL (2011) Expansion of a unique CD57(+)NKG2Chi natural killer cell subset during acute human cytomegalovirus infection. Proc Natl Acad Sci U S A 108:14725–14732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu LM, Zavitz CC, Chen B, Kianpour S, Wan Y, Stampfli MR (2007) Cigarette smoke impairs NK cell-dependent tumor immune surveillance. J Immunol 178:936–943

    Article  CAS  PubMed  Google Scholar 

  • Luetke-Eversloh M, Hammer Q, Durek P, Nordstrom K, Gasparoni G, Pink M, Hamann A, Walter J, Chang HD, Dong J, Romagnani C (2014) Human cytomegalovirus drives epigenetic imprinting of the IFNG locus in NKG2Chi natural killer cells. PLoS Pathog 10:e1004441

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lutz CT, Quinn LS (2012) Sarcopenia, obesity, and natural killer cell immune senescence in aging: altered cytokine levels as a common mechanism. Aging (Albany NY) 4:535–546

    Article  CAS  Google Scholar 

  • Lynch LA, O’Connell JM, Kwasnik AK, Cawood TJ, O’Farrelly C, O’Shea DB (2009) Are natural killer cells protecting the metabolically healthy obese patient? Obesity (Silver Spring) 17:601–605

    Article  CAS  Google Scholar 

  • Mariani E, Ravaglia G, Meneghetti A, Tarozzi A, Forti P, Maioli F, Boschi F, Facchini A (1998) Natural immunity and bone and muscle remodelling hormones in the elderly. Mech Ageing Dev 102:279–292

    Article  CAS  PubMed  Google Scholar 

  • Mariani E, Ravaglia G, Forti P, Meneghetti A, Tarozzi A, Maioli F, Boschi F, Pratelli L, Pizzoferrato A, Piras F, Facchini A (1999) Vitamin D, thyroid hormones and muscle mass influence natural killer (NK) innate immunity in healthy nonagenarians and centenarians. Clin Exp Immunol 116:19–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mariani F, Sena P, Magnani G, Mancini S, Palumbo C, Ponz De Leon M, RoncuccI L (2013) PLZF expression during colorectal cancer development and in normal colorectal mucosa according to body size, as marker of colorectal cancer risk. Sci World J 2013:630869

    Article  CAS  Google Scholar 

  • Marti A, Marcos A, Martinez JA (2001) Obesity and immune function relationships. Obes Rev 2:131–140

    Article  CAS  PubMed  Google Scholar 

  • Martinez-Rodriguez JE, Munne-Collado J, Rasal R, Cuadrado E, Roig L, Ois A, Muntasell A, Baro T, Alameda F, Roquer J, Lopez-Botet M (2013) Expansion of the NKG2C+ natural killer-cell subset is associated with high-risk carotid atherosclerotic plaques in seropositive patients for human cytomegalovirus. Arterioscler Thromb Vasc Biol 33:2653–2659

    Article  CAS  PubMed  Google Scholar 

  • Matsumura G (1990) Leu7 (HNK-1)-positive cells in peripheral blood and natural killer cell activity in patients with atopic dermatitis. Nihon Hifuka Gakkai Zasshi 100:57–62

    CAS  PubMed  Google Scholar 

  • Mori A, Sakurai H, Choo MK, Obi R, Koizumi K, Yoshida C, Shimada Y, Saiki I (2006) Severe pulmonary metastasis in obese and diabetic mice. Int J Cancer 119:2760–2767

    Article  CAS  PubMed  Google Scholar 

  • Morimoto K, Takeshita T, Inoue-Sakurai C, Maruyama S (2001) Lifestyles and mental health status are associated with natural killer cell and lymphokine-activated killer cell activities. Sci Total Environ 270:3–11

    Article  CAS  PubMed  Google Scholar 

  • Mysliwska J, Trzonkowski P, Szmit E, Brydak LB, Machala M, Mysliwski A (2004) Immunomodulating effect of influenza vaccination in the elderly differing in health status. Exp Gerontol 39:1447–1458

    Article  CAS  PubMed  Google Scholar 

  • Nave H, Mueller G, Siegmund B, Jacobs R, Stroh T, Schueler U, Hopfe M, Behrendt P, Buchenauer T, Pabst R, Brabant G (2008) Resistance of Janus kinase-2 dependent leptin signaling in natural killer (NK) cells: a novel mechanism of NK cell dysfunction in diet-induced obesity. Endocrinology 149:3370–3378

    Article  CAS  PubMed  Google Scholar 

  • Naylor C, Petri WA Jr (2016) Leptin regulation of immune responses. Trends Mol Med 22:88–98

    Article  CAS  PubMed  Google Scholar 

  • Nielsen CM, White MJ, Goodier MR, Riley EM (2013) Functional significance of CD57 expression on human NK cells and relevance to disease. Front Immunol 4:422

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • O’Rourke RW, Gaston GD, Meyer KA, White AE, Marks DL (2013) Adipose tissue NK cells manifest an activated phenotype in human obesity. Metabolism 62:1557–1561

    Article  PubMed  CAS  Google Scholar 

  • O’Shea D, Cawood TJ, O’Farrelly C, Lynch L (2010) Natural killer cells in obesity: impaired function and increased susceptibility to the effects of cigarette smoke. PLoS One 5:e8660

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ogata K, Yokose N, Tamura H, An E, Nakamura K, Dan K, Nomura T (1997) Natural killer cells in the late decades of human life. Clin Immunol Immunopathol 84:269–275

    Article  CAS  PubMed  Google Scholar 

  • Ogata K, An E, Shioi Y, Nakamura K, Luo S, Yokose N, Minami S, Dan K (2001) Association between natural killer cell activity and infection in immunologically normal elderly people. Clin Exp Immunol 124:392–397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ottaviani C, Nasorri F, Bedini C, De Pita O, Girolomoni G, Cavani A (2006) CD56brightCD16(−) NK cells accumulate in psoriatic skin in response to CXCL10 and CCL5 and exacerbate skin inflammation. Eur J Immunol 36:118–128

    Article  CAS  PubMed  Google Scholar 

  • Patel PS, Buras ED, Balasubramanyam A (2013) The role of the immune system in obesity and insulin resistance. J Obes 2013:616193

    PubMed  PubMed Central  Google Scholar 

  • Pawelec G, Solana R, Remarque E, Mariani E (1998) Impact of aging on innate immunity. J Leukoc Biol 64:703–712

    CAS  PubMed  Google Scholar 

  • Peeters A, Barendregt JJ, Willekens F, Mackenbach JP, Al Mamun A, Bonneux L, NEDCOM TNE, Demography Compression Of Morbidity Research, G (2003) Obesity in adulthood and its consequences for life expectancy: a life-table analysis. Ann Intern Med 138:24–32

    Article  PubMed  Google Scholar 

  • Perez LM, Pareja-Galeano H, Sanchis-Gomar F, Emanuele E, Lucia A, Galvez BG (2016) “Adipaging”: ageing and obesity share biological hallmarks related to a dysfunctional adipose tissue. J Physiol 594:3187–3207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Piatkiewicz P, Milek T, Bernat-Karpinska M, Ohams M, Czech A, Ciostek P (2013) The dysfunction of NK cells in patients with type 2 diabetes and colon cancer. Arch Immunol Ther Exp 61:245–253

    Article  CAS  Google Scholar 

  • Popko K, Gorska E (2015) The role of natural killer cells in pathogenesis of autoimmune diseases. Cent Eur J Immunol 40:470–476

    Article  PubMed  Google Scholar 

  • Ravaglia G, Forti P, Maioli F, Bastagli L, Facchini A, Mariani E, Savarino L, Sassi S, Cucinotta D, Lenaz G (2000) Effect of micronutrient status on natural killer cell immune function in healthy free-living subjects aged >/=90 y. Am J Clin Nutr 71:590–598

    CAS  PubMed  Google Scholar 

  • Renehan AG, Roberts DL, Dive C (2008) Obesity and cancer: pathophysiological and biological mechanisms. Arch Physiol Biochem 114:71–83

    Article  CAS  PubMed  Google Scholar 

  • Rolle A, Brodin P (2016) Immune adaptation to environmental influence: the case of NK cells and HCMV. Trends Immunol 37:233–243

    Article  PubMed  CAS  Google Scholar 

  • Rose S, Stansky E, Dagur PK, Samsel L, Weiner E, Jahanshad A, Doveikis J, Naik HB, Playford MP, Mccoy JP, Mehta NN (2014) Characterization of immune cells in psoriatic adipose tissue. J Transl Med 12:258

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Salvioli S, Monti D, Lanzarini C, Conte M, Pirazzini C, Bacalini MG, Garagnani P, Giuliani C, Fontanesi E, Ostan R, Bucci L, Sevini F, Yani SL, Barbieri A, Lomartire L, Borelli V, Vianello D, Bellavista E, Martucci M, Cevenini E, Pini E, Scurti M, Biondi F, Santoro A, Capri M, Franceschi C (2013) Immune system, cell senescence, aging and longevity – inflamm-aging reappraised. Curr Pharm Des 19:1675–1679

    CAS  PubMed  Google Scholar 

  • Sanchez-Correa B, Bergua JM, Campos C, Gayoso I, Arcos MJ, Banas H, Morgado S, Casado JG, Solana R, Tarazona R (2013) Cytokine profiles in acute myeloid leukemia patients at diagnosis: survival is inversely correlated with IL-6 and directly correlated with IL-10 levels. Cytokine 61:885–891

    Article  CAS  PubMed  Google Scholar 

  • Sanchez-Correa B, Campos C, Pera A, Bergua JM, Arcos MJ, BANAS H, Casado JG, Morgado S, Duran E, Solana R, Tarazona R (2016) Natural killer cell immunosenescence in acute myeloid leukaemia patients: new targets for immunotherapeutic strategies? Cancer Immunol Immunother 65:453–463

    Article  CAS  PubMed  Google Scholar 

  • Sansoni P, Brianti V, Fagnoni F, Snelli G, Marcato A, Passeri G, Monti D, Cossarizza A, Franceschi C (1992) NK cell activity and T-lymphocyte proliferation in healthy centenarians. Ann N Y Acad Sci 663:505–507

    Article  CAS  PubMed  Google Scholar 

  • Sansoni P, Cossarizza A, Brianti V, Fagnoni F, Snelli G, Monti D, Marcato A, Passeri G, Ortolani C, Forti E et al (1993) Lymphocyte subsets and natural killer cell activity in healthy old people and centenarians. Blood 82:2767–2773

    CAS  PubMed  Google Scholar 

  • Schlums H, Cichocki F, Tesi B, Theorell J, Beziat V, Holmes TD, Han H, Chiang SC, Foley B, Mattsson K, Larsson S, Schaffer M, Malmberg KJ, Ljunggren HG, Miller JS, Bryceson YT (2015) Cytomegalovirus infection drives adaptive epigenetic diversification of NK cells with altered signaling and effector function. Immunity 42:443–456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seijkens T, Kusters P, Chatzigeorgiou A, Chavakis T, Lutgens E (2014) Immune cell crosstalk in obesity: a key role for costimulation? Diabetes 63:3982–3991

    Article  CAS  PubMed  Google Scholar 

  • Smith AG, Sheridan PA, Harp JB, Beck MA (2007) Diet-induced obese mice have increased mortality and altered immune responses when infected with influenza virus. J Nutr 137:1236–1243

    CAS  PubMed  Google Scholar 

  • Solana R, Tarazona R, Aiello AE, Akbar AN, Appay V, Beswick M, Bosch JA, Campos C, Cantisan S, Cicin-Sain L, Derhovanessian E, Ferrando-Martinez S, Frasca D, Fulop T, Govind S, Grubeck-Loebenstein B, Hill A, Hurme M, Kern F, Larbi A, Lopez-Botet M, Maier AB, Mcelhaney JE, Moss P, Naumova E, Nikolich-Zugich J, Pera A, Rector JL, Riddell N, Sanchez-Correa B, Sansoni P, Sauce D, Van Lier R, Wang GC, Wills MR, Zielinski M, Pawelec G (2012) CMV and immunosenescence: from basics to clinics. Immun Ageing 9:23

    Article  PubMed  PubMed Central  Google Scholar 

  • Solana R, Campos C, Pera A, Tarazona R (2014) Shaping of NK cell subsets by aging. Curr Opin Immunol 29:56–61

    Article  CAS  PubMed  Google Scholar 

  • Strindhall J, Skog M, Ernerudh J, Bengner M, Lofgren S, Matussek A, Nilsson BO, Wikby A (2013) The inverted CD4/CD8 ratio and associated parameters in 66-year-old individuals: the Swedish HEXA immune study. Age (Dordr) 35:985–991

    Article  CAS  Google Scholar 

  • Strioga M, Pasukoniene V, Characiejus D (2011) CD8+ CD28- and CD8+ CD57+ T cells and their role in health and disease. Immunology 134:17–32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tae Yu H, Youn JC, Lee J, Park S, Chi HS, Lee J, Choi C, Park S, Choi D, Ha JW, Shin EC (2015) Characterization of CD8(+)CD57(+) T cells in patients with acute myocardial infarction. Cell Mol Immunol 12:466–473

    Article  CAS  PubMed  Google Scholar 

  • Tian Z, Sun R, Wei H, Gao B (2002) Impaired natural killer (NK) cell activity in leptin receptor deficient mice: leptin as a critical regulator in NK cell development and activation. Biochem Biophys Res Commun 298:297–302

    Article  CAS  PubMed  Google Scholar 

  • Viel S, Besson L, Charrier E, Marcais A, Disse E, Bienvenu J, Walzer T, Dumontet C (2016) Alteration of natural killer cell phenotype and function in obese individuals. Clin Immunol 177:12–17

    Article  PubMed  CAS  Google Scholar 

  • Vona-Davis L, Rose DP (2007) Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression. Endocr Relat Cancer 14:189–206

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Geiger H, Rudolph KL (2011) Immunoaging induced by hematopoietic stem cell aging. Curr Opin Immunol 23:532–536

    Article  CAS  PubMed  Google Scholar 

  • Wensveen FM, Valentic S, Sestan M, Turk Wensveen T, Polic B (2015) The “big bang” in obese fat: events initiating obesity-induced adipose tissue inflammation. Eur J Immunol 45:2446–2456

    Article  CAS  PubMed  Google Scholar 

  • Wikby A, Maxson P, Olsson J, Johansson B, Ferguson FG (1998) Changes in CD8 and CD4 lymphocyte subsets, T cell proliferation responses and non-survival in the very old: the Swedish longitudinal OCTO-immune study. Mech Ageing Dev 102:187–198

    Article  CAS  PubMed  Google Scholar 

  • Wikby A, Johansson B, Olsson J, Lofgren S, Nilsson BO, Ferguson F (2002) Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study. Exp Gerontol 37:445–453

    Article  CAS  PubMed  Google Scholar 

  • Wrann CD, Laue T, Hubner L, Kuhlmann S, Jacobs R, Goudeva L, Nave H (2012) Short-term and long-term leptin exposure differentially affect human natural killer cell immune functions. Am J Physiol Endocrinol Metab 302:E108–E116

    Article  CAS  PubMed  Google Scholar 

  • Ye J (2015) Beneficial metabolic activities of inflammatory cytokine interleukin 15 in obesity and type 2 diabetes. Front Med 9:139–145

    Article  PubMed  Google Scholar 

  • Zhao Y, Sun R, You L, Gao C, Tian Z (2003) Expression of leptin receptors and response to leptin stimulation of human natural killer cell lines. Biochem Biophys Res Commun 300:247–252

    Article  CAS  PubMed  Google Scholar 

  • Zhao Y, Forst CV, Sayegh CE, Wang IM, Yang X, Zhang B (2016) Molecular and genetic inflammation networks in major human diseases. Mol BioSyst 12(8):2318–2341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We apologize to our colleagues whose work was not cited due to space limitations. This work was supported by grants PS09/00723 and PI13/02691 (to RS) from Spanish Ministry of Health and CTS-208 from Junta de Andalucia (to RS) and SAF2009-09711 and SAF2013-46161-R (to RT) from the Ministry of Economy and Competitiveness of Spain and grants to INPATT research group (GR10104 and GR15183) from Junta de Extremadura and University of Extremadura (to RT) cofinanced by European Regional Development Funds (FEDER).

Author information

Authors and Affiliations

  1. Brighton and Sussex Medical School, University of Sussex, Brighton, UK

    Alejandra Pera

  2. Maimonides Biomedicine Institute of Cordoba (IMIBIC)-Reina Sofia Hospital-University of Cordoba, Cordoba, Spain

    Alejandra Pera, Carmen Campos, Fakhri Hassouneh & Nelson Lopez-Sejas

  3. Research Centre in Molecular Biology of Chronic Diseases (CIBIMEC), CUSUR, University of Guadalajara, Ciudad Guzman, Jalisco, Mexico

    María Luisa Pita-López

  4. Immunology Unit, Department of Physiology, University of Extremadura, Cáceres, Spain

    Beatriz Sánchez-Correa, Raquel Tarazona & Rafael Solana

Authors
  1. Alejandra Pera
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. María Luisa Pita-López
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carmen Campos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fakhri Hassouneh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nelson Lopez-Sejas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Beatriz Sánchez-Correa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Raquel Tarazona
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rafael Solana
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alejandra Pera .

Editor information

Editors and Affiliations

  1. Division of Geriatrics Research Center on Aging, University of Sherbrooke Dept. of Medicine, Sherbrooke, Québec, Canada

    Tamas Fulop

  2. Dept 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

Rights and permissions

Reprints and permissions

Copyright information

© 2018 The Author(s)

About this entry

Cite this entry

Pera, A. et al. (2018). Natural Killer Cells and Health Status: Age, CMV Infection, and Obesity. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook of Immunosenescence. Springer, Cham. https://doi.org/10.1007/978-3-319-64597-1_127-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-64597-1_127-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-64597-1

  • Online ISBN: 978-3-319-64597-1

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Chapter history

  1. Latest

    Natural Killer Cells and Health Status: Age, CMV Infection, and Obesity
    Published:
    16 February 2018

    DOI: https://doi.org/10.1007/978-3-319-64597-1_127-2

  2. Original

    Natural Killer Cells and Health Status: Age, CMV Infection, and Obesity
    Published:
    13 October 2017

    DOI: https://doi.org/10.1007/978-3-319-64597-1_127-1

Search

Navigation