Chronic Inflammation in Immune Aging: Role of Pattern Recognition Receptor Crosstalk with the Telomere Complex?
Status PubMed-not-MEDLINE Language English Country Switzerland Media electronic-ecollection
Document type Journal Article, Review
PubMed
28928745
PubMed Central
PMC5591428
DOI
10.3389/fimmu.2017.01078
Knihovny.cz E-resources
- Keywords
- NF-κB, inflammaging, myelopoiesis, pattern recognition receptor signaling, telomere shortening, toll-like receptor signaling,
- Publication type
- Journal Article MeSH
- Review MeSH
Age-related decline in immunity is characterized by stem cell exhaustion, telomere shortening, and disruption of cell-to-cell communication, leading to increased patient risk of disease. Recent data have demonstrated that chronic inflammation exerts a strong influence on immune aging and is closely correlated with telomere length in a range of major pathologies. The current review discusses the impact of inflammation on immune aging, the likely molecular mediators of this process, and the various disease states that have been linked with immunosenescence. Emerging findings implicate NF-κB, the major driver of inflammatory signaling, in several processes that regulate telomere maintenance and/or telomerase activity. While prolonged triggering of pattern recognition receptors is now known to promote immunosenescence, it remains unclear how this process is linked with the telomere complex or telomerase activity. Indeed, enzymatic control of telomere length has been studied for many decades, but alternative roles of telomerase and potential influences on inflammatory responses are only now beginning to emerge. Crosstalk between these pathways may prove to be a key molecular mechanism of immunosenescence. Understanding how components of immune aging interact and modify host protection against pathogens and tumors will be essential for the design of new vaccines and therapies for a wide range of clinical scenarios.
Cellular and Molecular Immunoregulation Group St Anne's University Hospital Brno Brno Czechia
Department of Biology Faculty of Medicine Masaryk University Czechia
Pediatric Hematology and Oncology University Hospital Brno Brno Czechia
Pediatric Oncology Translational Research St Anne's University Hospital Brno Brno Czechia
See more in PubMed
Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell (2013) 153(6):1194–217.10.1016/j.cell.2013.05.039 PubMed DOI PMC
Kirkwood TB. Understanding the odd science of aging. Cell (2005) 120(4):437–47.10.1016/j.cell.2005.01.027 PubMed DOI
Chiu CP, Dragowska W, Kim NW, Vaziri H, Yui J, Thomas TE, et al. Differential expression of telomerase activity in hematopoietic progenitors from adult human bone marrow. Stem Cells (1996) 14(2):239–48.10.1002/stem.140239 PubMed DOI
Engelhardt M, Kumar R, Albanell J, Pettengell R, Han W, Moore MA. Telomerase regulation, cell cycle, and telomere stability in primitive hematopoietic cells. Blood (1997) 90(1):182–93. PubMed
Plunkett FJ, Franzese O, Finney HM, Fletcher JM, Belaramani LL, Salmon M, et al. The loss of telomerase activity in highly differentiated CD8+CD28-CD27- T cells is associated with decreased Akt (Ser473) phosphorylation. J Immunol (2007) 178(12):7710–9.10.4049/jimmunol.178.12.7710 PubMed DOI
Akbar AN, Vukmanovic-Stejic M. Telomerase in T lymphocytes: use it and lose it? J Immunol (2007) 178(11):6689–94.10.4049/jimmunol.178.11.6689 PubMed DOI
Palm W, de Lange T. How shelterin protects mammalian telomeres. Annu Rev Genet (2008) 42:301–34.10.1146/annurev.genet.41.110306.130350 PubMed DOI
Agarwal S, Busse PJ. Innate and adaptive immunosenescence. Ann Allergy Asthma Immunol (2010) 104(3):183–90.10.1016/j.anai.2009.11.009 PubMed DOI
Pulko V, Davies JS, Martinez C, Lanteri MC, Busch MP, Diamond MS, et al. Human memory T cells with a naive phenotype accumulate with aging and respond to persistent viruses. Nat Immunol (2016) 17(8):966–75.10.1038/ni.3483 PubMed DOI PMC
Wikby A, Nilsson BO, Forsey R, Thompson J, Strindhall J, Lofgren S, et al. The immune risk phenotype is associated with IL-6 in the terminal decline stage: findings from the Swedish NONA immune longitudinal study of very late life functioning. Mech Ageing Dev (2006) 127(8):695–704.10.1016/j.mad.2006.04.003 PubMed DOI
Wikby A, Ferguson F, Forsey R, Thompson J, Strindhall J, Lofgren S, et al. An immune risk phenotype, cognitive impairment, and survival in very late life: impact of allostatic load in Swedish octogenarian and nonagenarian humans. J Gerontol A Biol Sci Med Sci (2005) 60(5):556–65.10.1093/gerona/60.5.556 PubMed DOI
Panda A, Arjona A, Sapey E, Bai F, Fikrig E, Montgomery RR, et al. Human innate immunosenescence: causes and consequences for immunity in old age. Trends Immunol (2009) 30(7):325–33.10.1016/j.it.2009.05.004 PubMed DOI PMC
Fulop T, Larbi A, Douziech N, Fortin C, Guerard KP, Lesur O, et al. Signal transduction and functional changes in neutrophils with aging. Aging Cell (2004) 3(4):217–26.10.1111/j.1474-9728.2004.00110.x PubMed DOI
Morrisette-Thomas V, Cohen AA, Fulop T, Riesco E, Legault V, Li Q, et al. Inflamm-aging does not simply reflect increases in pro-inflammatory markers. Mech Ageing Dev (2014) 139:49–57.10.1016/j.mad.2014.06.005 PubMed DOI PMC
De Martinis M, Franceschi C, Monti D, Ginaldi L. Inflammation markers predicting frailty and mortality in the elderly. Exp Mol Pathol (2006) 80(3):219–27.10.1016/j.yexmp.2005.11.004 PubMed DOI
Chung SS, Wu Y, Okobi Q, Adekoya D, Atefi M, Clarke O, et al. Proinflammatory cytokines IL-6 and TNF-α increased telomerase activity through NF-κB/STAT1/STAT3 activation, and withaferin A inhibited the signaling in colorectal cancer cells. Mediators Inflamm (2017) 2017:5958429.10.1155/2017/5958429 PubMed DOI PMC
Zeng Y, Nie C, Min J, Liu X, Li M, Chen H, et al. Novel loci and pathways significantly associated with longevity. Sci Rep (2016) 6:21243.10.1038/srep21243 PubMed DOI PMC
Bonafe M, Olivieri F, Cavallone L, Giovagnetti S, Mayegiani F, Cardelli M, et al. A gender-dependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity. Eur J Immunol (2001) 31(8):2357–61.10.1002/1521-4141(200108)31:8<2357::AID-IMMU2357>3.0.CO;2-X PubMed DOI
Scheinecker C, Smolen J, Yasothan U, Stoll J, Kirkpatrick P. Tocilizumab. Nat Rev Drug Discov (2009) 8(4):273–4.10.1038/nrd2863 PubMed DOI
Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, et al. Inflamm-aging. An evolutionary perspective on immunosenescence.Ann N Y Acad Sci (2000) 908:244–54.10.1111/j.1749-6632.2000.tb06651.x PubMed DOI
Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, et al. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev (2007) 128(1):92–105.10.1016/j.mad.2006.11.016 PubMed DOI
Tu W, Rao S. Mechanisms underlying T cell immunosenescence: aging and cytomegalovirus infection. Front Microbiol (2016) 7:2111.10.3389/fmicb.2016.02111 PubMed DOI PMC
Peres A, Bauer M, da Cruz IB, Nardi NB, Chies JA. Immunophenotyping and T-cell proliferative capacity in a healthy aged population. Biogerontology (2003) 4(5):289–96.10.1023/A:1026282917406 PubMed DOI
Panda A, Qian F, Mohanty S, van Duin D, Newman FK, Zhang L, et al. Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response. J Immunol (2010) 184(5):2518–27.10.4049/jimmunol.0901022 PubMed DOI PMC
Fulop T, Larbi A, Witkowski JM, Kotb R, Hirokawa K, Pawelec G. Immunosenescence and cancer. Crit Rev Oncog (2013) 18(6):489–513.10.1615/CritRevOncog.2013010597 PubMed DOI
Solana R, Tarazona R, Gayoso I, Lesur O, Dupuis G, Fulop T. Innate immunosenescence: effect of aging on cells and receptors of the innate immune system in humans. Semin Immunol (2012) 24(5):331–41.10.1016/j.smim.2012.04.008 PubMed DOI
Koch S, Larbi A, Ozcelik D, Solana R, Gouttefangeas C, Attig S, et al. Cytomegalovirus infection: a driving force in human T cell immunosenescence. Ann N Y Acad Sci (2007) 1114:23–35.10.1196/annals.1396.043 PubMed DOI
Vasto S, Colonna-Romano G, Larbi A, Wikby A, Caruso C, Pawelec G. Role of persistent CMV infection in configuring T cell immunity in the elderly. Immun Ageing (2007) 4:2.10.1186/1742-4933-4-2 PubMed DOI PMC
Jurk D, Wilson C, Passos JF, Oakley F, Correia-Melo C, Greaves L, et al. Chronic inflammation induces telomere dysfunction and accelerates ageing in mice. Nat Commun (2014) 2:4172.10.1038/ncomms5172 PubMed DOI PMC
Sebastian C, Herrero C, Serra M, Lloberas J, Blasco MA, Celada A. Telomere shortening and oxidative stress in aged macrophages results in impaired STAT5a phosphorylation. J Immunol (2009) 183(4):2356–64.10.4049/jimmunol.0901131 PubMed DOI
Zhu Y, Armstrong JL, Tchkonia T, Kirkland JL. Cellular senescence and the senescent secretory phenotype in age-related chronic diseases. Curr Opin Clin Nutr Metab Care (2014) 17(4):324–8.10.1097/MCO.0000000000000065 PubMed DOI
von Zglinicki T, Martin-Ruiz CM. Telomeres as biomarkers for ageing and age-related diseases. Curr Mol Med (2005) 5(2):197–203.10.2174/1566524053586545 PubMed DOI
Franceschi C, Garagnani P, Vitale G, Capri M, Salvioli S. Inflammaging and ‘Garb-aging’. Trends Endocrinol Metab (2017) 28(3):199–212.10.1016/j.tem.2016.09.005 PubMed DOI
Kordinas V, Ioannidis A, Chatzipanagiotou S. The telomere/telomerase system in chronic inflammatory diseases. Cause or effect? Genes (Basel) (2016) 7(9):E60.10.3390/genes7090060 PubMed DOI PMC
Lepperdinger G. Inflammation and mesenchymal stem cell aging. Curr Opin Immunol (2011) 23(4):518–24.10.1016/j.coi.2011.05.007 PubMed DOI PMC
Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature (2010) 464(7285):104–7.10.1038/nature08780 PubMed DOI PMC
Pinti M, Cevenini E, Nasi M, De Biasi S, Salvioli S, Monti D, et al. Circulating mitochondrial DNA increases with age and is a familiar trait: implications for “inflamm-aging”. Eur J Immunol (2014) 44(5):1552–62.10.1002/eji.201343921 PubMed DOI
Gupta GK, Agrawal DK. CpG oligodeoxynucleotides as TLR9 agonists: therapeutic application in allergy and asthma. BioDrugs (2010) 24(4):225–35.10.2165/11536140-000000000-00000 PubMed DOI
Wang Z, Lieberman PM. The crosstalk of telomere dysfunction and inflammation through cell-free TERRA containing exosomes. RNA Biol (2016) 13(8):690–5.10.1080/15476286.2016.1203503 PubMed DOI PMC
Lin L, Park S, Lakatta EG. RAGE signaling in inflammation and arterial aging. Front Biosci (Landmark Ed) (2009) 14:1403–13.10.2741/3315 PubMed DOI PMC
Samy RP, Lim LH. DAMPs and influenza virus infection in ageing. Ageing Res Rev (2015) 24(Pt A):83–97.10.1016/j.arr.2015.07.005 PubMed DOI
Seneviratne AN, Sivagurunathan B, Monaco C. Toll-like receptors and macrophage activation in atherosclerosis. Clin Chim Acta (2012) 413(1–2):3–14.10.1016/j.cca.2011.08.021 PubMed DOI
Hovland A, Jonasson L, Garred P, Yndestad A, Aukrust P, Lappegard KT, et al. The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis. Atherosclerosis (2015) 241(2):480–94.10.1016/j.atherosclerosis.2015.05.038 PubMed DOI
Falck-Hansen M, Kassiteridi C, Monaco C. Toll-like receptors in atherosclerosis. Int J Mol Sci (2013) 14(7):14008–23.10.3390/ijms140714008 PubMed DOI PMC
Meng X, Ao L, Song Y, Babu A, Yang X, Wang M, et al. Expression of functional toll-like receptors 2 and 4 in human aortic valve interstitial cells: potential roles in aortic valve inflammation and stenosis. Am J Physiol Cell Physiol (2008) 294(1):C29–35.10.1152/ajpcell.00137.2007 PubMed DOI
Fyhrquist F, Saijonmaa O, Strandberg T. The roles of senescence and telomere shortening in cardiovascular disease. Nat Rev Cardiol (2013) 10(5):274–83.10.1038/nrcardio.2013.30 PubMed DOI
Gizard F, Heywood EB, Findeisen HM, Zhao Y, Jones KL, Cudejko C, et al. Telomerase activation in atherosclerosis and induction of telomerase reverse transcriptase expression by inflammatory stimuli in macrophages. Arterioscler Thromb Vasc Biol (2011) 31(2):245–52.10.1161/ATVBAHA.110.219808 PubMed DOI PMC
Liu SC, Wang SS, Wu MZ, Wu DC, Yu FJ, Chen WJ, et al. Activation of telomerase and expression of human telomerase reverse transcriptase in coronary atherosclerosis. Cardiovasc Pathol (2005) 14(5):232–40.10.1016/j.carpath.2005.05.006 PubMed DOI
Wagner KB, Felix SB, Riad A. Innate immune receptors in heart failure: side effect or potential therapeutic target? World J Cardiol (2014) 6(8):791–801.10.4330/wjc.v6.i8.791 PubMed DOI PMC
van der Harst P, van der Steege G, de Boer RA, Voors AA, Hall AS, Mulder MJ, et al. Telomere length of circulating leukocytes is decreased in patients with chronic heart failure. J Am Coll Cardiol (2007) 49(13):1459–64.10.1016/j.jacc.2007.01.027 PubMed DOI
Bezemer GF, Sagar S, van Bergenhenegouwen J, Georgiou NA, Garssen J, Kraneveld AD, et al. Dual role of toll-like receptors in asthma and chronic obstructive pulmonary disease. Pharmacol Rev (2012) 64(2):337–58.10.1124/pr.111.004622 PubMed DOI
Cordoba-Lanus E, Cazorla-Rivero S, Espinoza-Jimenez A, de-Torres JP, Pajares MJ, Aguirre-Jaime A, et al. Telomere shortening and accelerated aging in COPD: findings from the BODE cohort. Respir Res (2017) 18(1):59.10.1186/s12931-017-0547-4 PubMed DOI PMC
Houben JM, Mercken EM, Ketelslegers HB, Bast A, Wouters EF, Hageman GJ, et al. Telomere shortening in chronic obstructive pulmonary disease. Respir Med (2009) 103(2):230–6.10.1016/j.rmed.2008.09.003 PubMed DOI
Gabrilovich MI, Walrath J, van Lunteren J, Nethery D, Seifu M, Kern JA, et al. Disordered toll-like receptor 2 responses in the pathogenesis of pulmonary sarcoidosis. Clin Exp Immunol (2013) 173(3):512–22.10.1111/cei.12138 PubMed DOI PMC
Guan JZ, Maeda T, Sugano M, Oyama J, Higuchi Y, Suzuki T, et al. An analysis of telomere length in sarcoidosis. J Gerontol A Biol Sci Med Sci (2007) 62(11):1199–203.10.1093/gerona/62.11.1199 PubMed DOI
Maeda T, Guan JZ, Higuchi Y, Oyama J, Makino N. Aging-related alterations of subtelomeric methylation in sarcoidosis patients. J Gerontol A Biol Sci Med Sci (2009) 64(7):752–60.10.1093/gerona/glp049 PubMed DOI
Xiao X, Zhao P, Rodriguez-Pinto D, Qi D, Henegariu O, Alexopoulou L, et al. Inflammatory regulation by TLR3 in acute hepatitis. J Immunol (2009) 183(6):3712–9.10.4049/jimmunol.0901221 PubMed DOI PMC
Broering R, Montag M, Jiang M, Lu M, Sowa JP, Kleinehr K, et al. Corticosteroids shift the toll-like receptor response pattern of primary-isolated murine liver cells from an inflammatory to an anti-inflammatory state. Int Immunol (2011) 23(9):537–44.10.1093/intimm/dxr048 PubMed DOI
Kim S, Park S, Kim B, Kwon J. Toll-like receptor 7 affects the pathogenesis of non-alcoholic fatty liver disease. Sci Rep (2016) 6:27849.10.1038/srep27849 PubMed DOI PMC
Mencin A, Kluwe J, Schwabe RF. Toll-like receptors as targets in chronic liver diseases. Gut (2009) 58(5):704–20.10.1136/gut.2008.156307 PubMed DOI PMC
Kitada T, Seki S, Kawakita N, Kuroki T, Monna T. Telomere shortening in chronic liver diseases. Biochem Biophys Res Commun (1995) 211(1):33–9.10.1006/bbrc.1995.1774 PubMed DOI
Mao TK, Lian ZX, Selmi C, Ichiki Y, Ashwood P, Ansari AA, et al. Altered monocyte responses to defined TLR ligands in patients with primary biliary cirrhosis. Hepatology (2005) 42(4):802–8.10.1002/hep.20859 PubMed DOI
Sasaki M, Ikeda H, Yamaguchi J, Nakada S, Nakanuma Y. Telomere shortening in the damaged small bile ducts in primary biliary cirrhosis reflects ongoing cellular senescence. Hepatology (2008) 48(1):186–95.10.1002/hep.22348 PubMed DOI
Stanislawowski M, Wierzbicki PM, Golab A, Adrych K, Kartanowicz D, Wypych J, et al. Decreased toll-like receptor-5 (TLR-5) expression in the mucosa of ulcerative colitis patients. J Physiol Pharmacol (2009) 60(Suppl 4):71–5. PubMed
Franchimont D, Vermeire S, El Housni H, Pierik M, Van Steen K, Gustot T, et al. Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn’s disease and ulcerative colitis. Gut (2004) 53(7):987–92.10.1136/gut.2003.030205 PubMed DOI PMC
Friis-Ottessen M, Bendix L, Kolvraa S, Norheim-Andersen S, De Angelis PM, Clausen OP. Telomere shortening correlates to dysplasia but not to DNA aneuploidy in longstanding ulcerative colitis. BMC Gastroenterol (2014) 14:8.10.1186/1471-230X-14-8 PubMed DOI PMC
Risques RA, Lai LA, Brentnall TA, Li L, Feng Z, Gallaher J, et al. Ulcerative colitis is a disease of accelerated colon aging: evidence from telomere attrition and DNA damage. Gastroenterology (2008) 135(2):410–8.10.1053/j.gastro.2008.04.008 PubMed DOI PMC
O’Sullivan JN, Bronner MP, Brentnall TA, Finley JC, Shen WT, Emerson S, et al. Chromosomal instability in ulcerative colitis is related to telomere shortening. Nat Genet (2002) 32(2):280–4.10.1038/ng989 PubMed DOI
Kinouchi Y, Hiwatashi N, Chida M, Nagashima F, Takagi S, Maekawa H, et al. Telomere shortening in the colonic mucosa of patients with ulcerative colitis. J Gastroenterol (1998) 33(3):343–8.10.1007/s005350050094 PubMed DOI
Holzmann K, Klump B, Weis-Klemm M, Hsieh CJ, Borchard F, Gregor M, et al. Telomerase activity in long-standing ulcerative colitis. Anticancer Res (2000) 20(5C):3951–5. PubMed
Szebeni B, Veres G, Dezsofi A, Rusai K, Vannay A, Bokodi G, et al. Increased mucosal expression of toll-like receptor (TLR)2 and TLR4 in coeliac disease. J Pediatr Gastroenterol Nutr (2007) 45(2):187–93.10.1097/MPG.0b013e318064514a PubMed DOI
Kamycheva E, Goto T, Camargo CA, Jr. Celiac disease autoimmunity is associated with leukocyte telomere shortening in older adults: the U.S. National Health and Nutrition Examination Survey. Exp Gerontol (2017) 89:64–8.10.1016/j.exger.2017.01.003 PubMed DOI
Rayavarapu S, Coley W, Kinder TB, Nagaraju K. Idiopathic inflammatory myopathies: pathogenic mechanisms of muscle weakness. Skelet Muscle (2013) 3(1):13.10.1186/2044-5040-3-13 PubMed DOI PMC
Ponsot E, Echaniz-Laguna A, Delis AM, Kadi F. Telomere length and regulatory proteins in human skeletal muscle with and without ongoing regenerative cycles. Exp Physiol (2012) 97(6):774–84.10.1113/expphysiol.2011.063818 PubMed DOI
Thwaites R, Chamberlain G, Sacre S. Emerging role of endosomal toll-like receptors in rheumatoid arthritis. Front Immunol (2014) 5:1.10.3389/fimmu.2014.00001 PubMed DOI PMC
Huang QQ, Pope RM. The role of toll-like receptors in rheumatoid arthritis. Curr Rheumatol Rep (2009) 11(5):357–64.10.1007/s11926-009-0051-z PubMed DOI PMC
Steer SE, Williams FM, Kato B, Gardner JP, Norman PJ, Hall MA, et al. Reduced telomere length in rheumatoid arthritis is independent of disease activity and duration. Ann Rheum Dis (2007) 66(4):476–80.10.1136/ard.2006.059188 PubMed DOI PMC
Fujii H, Shao L, Colmegna I, Goronzy JJ, Weyand CM. Telomerase insufficiency in rheumatoid arthritis. Proc Natl Acad Sci U S A (2009) 106(11):4360–5.10.1073/pnas.0811332106 PubMed DOI PMC
Yudoh K, Matsuno H, Nezuka T, Kimura T. Different mechanisms of synovial hyperplasia in rheumatoid arthritis and pigmented villonodular synovitis: the role of telomerase activity in synovial proliferation. Arthritis Rheum (1999) 42(4):669–77.10.1002/1529-0131(199904)42:4<669::AID-ANR9>3.0.CO;2-V PubMed DOI
Tarhan F, Vural F, Kosova B, Aksu K, Cogulu O, Keser G, et al. Telomerase activity in connective tissue diseases: elevated in rheumatoid arthritis, but markedly decreased in systemic sclerosis. Rheumatol Int (2008) 28(6):579–83.10.1007/s00296-007-0472-9 PubMed DOI
Kirchner M, Sonnenschein A, Schoofs S, Schmidtke P, Umlauf VN, Mannhardt-Laakmann W. Surface expression and genotypes of toll-like receptors 2 and 4 in patients with juvenile idiopathic arthritis and systemic lupus erythematosus. Pediatr Rheumatol Online J (2013) 11(1):9.10.1186/1546-0096-11-9 PubMed DOI PMC
Prelog M, Schwarzenbrunner N, Sailer-Hock M, Kern H, Klein-Franke A, Ausserlechner MJ, et al. Premature aging of the immune system in children with juvenile idiopathic arthritis. Arthritis Rheum (2008) 58(7):2153–62.10.1002/art.23599 PubMed DOI
Picarelli MM, Danzmann LC, Grun LK, Junior NTR, Lavandovsky P, Guma F, et al. Arterial stiffness by oscillometric device and telomere length in juvenile idiopathic arthritis with no cardiovascular risk factors: a cross-sectional study. Pediatr Rheumatol Online J (2017) 15(1):34.10.1186/s12969-017-0165-1 PubMed DOI PMC
Ciechomska M, Cant R, Finnigan J, van Laar JM, O’Reilly S. Role of toll-like receptors in systemic sclerosis. Expert Rev Mol Med (2013) 15:e9.10.1017/erm.2013.10 PubMed DOI
Bhattacharyya S, Varga J. Emerging roles of innate immune signaling and toll-like receptors in fibrosis and systemic sclerosis. Curr Rheumatol Rep (2015) 17(1):474.10.1007/s11926-014-0474-z PubMed DOI
Yoshizaki A, Iwata Y, Komura K, Ogawa F, Hara T, Muroi E, et al. CD19 regulates skin and lung fibrosis via toll-like receptor signaling in a model of bleomycin-induced scleroderma. Am J Pathol (2008) 172(6):1650–63.10.2353/ajpath.2008.071049 PubMed DOI PMC
Artlett CM, Black CM, Briggs DC, Stevens CO, Welsh KI. Telomere reduction in scleroderma patients: a possible cause for chromosomal instability. Br J Rheumatol (1996) 35(8):732–7.10.1093/rheumatology/35.8.732 PubMed DOI
Katayama Y, Kohriyama K. Telomerase activity in peripheral blood mononuclear cells of systemic connective tissue diseases. J Rheumatol (2001) 28(2):288–91. PubMed
Pan HF, Wu GC, Li WP, Li XP, Ye DQ. High mobility group box 1: a potential therapeutic target for systemic lupus erythematosus. Mol Biol Rep (2010) 37(3):1191–5.10.1007/s11033-009-9485-7 PubMed DOI
Celhar T, Fairhurst AM. Toll-like receptors in systemic lupus erythematosus: potential for personalized treatment. Front Pharmacol (2014) 5:265.10.3389/fphar.2014.00265 PubMed DOI PMC
Rahman AH, Eisenberg RA. The role of toll-like receptors in systemic lupus erythematosus. Springer Semin Immunopathol (2006) 28(2):131–43.10.1007/s00281-006-0034-3 PubMed DOI
Haque S, Rakieh C, Marriage F, Ho P, Gorodkin R, Teh LS, et al. Shortened telomere length in patients with systemic lupus erythematosus. Arthritis Rheum (2013) 65(5):1319–23.10.1002/art.37895 PubMed DOI
Honda M, Mengesha E, Albano S, Nichols WS, Wallace DJ, Metzger A, et al. Telomere shortening and decreased replicative potential, contrasted by continued proliferation of telomerase-positive CD8+CD28(lo) T cells in patients with systemic lupus erythematosus. Clin Immunol (2001) 99(2):211–21.10.1006/clim.2001.5023 PubMed DOI
O’Connor PM, Lapointe TK, Jackson S, Beck PL, Jones NL, Buret AG. Helicobacter pylori activates calpain via toll-like receptor 2 to disrupt adherens junctions in human gastric epithelial cells. Infect Immun (2011) 79(10):3887–94.10.1128/IAI.05109-11 PubMed DOI PMC
Ishihara S, Rumi MA, Kadowaki Y, Ortega-Cava CF, Yuki T, Yoshino N, et al. Essential role of MD-2 in TLR4-dependent signaling during Helicobacter pylori-associated gastritis. J Immunol (2004) 173(2):1406–16.10.4049/jimmunol.173.2.1406 PubMed DOI
Allison CC, Kufer TA, Kremmer E, Kaparakis M, Ferrero RL. Helicobacter pylori induces MAPK phosphorylation and AP-1 activation via a NOD1-dependent mechanism. J Immunol (2009) 183(12):8099–109.10.4049/jimmunol.0900664 PubMed DOI
Lee WP, Hou MC, Lan KH, Li CP, Chao Y, Lin HC, et al. Helicobacter pylori-induced chronic inflammation causes telomere shortening of gastric mucosa by promoting PARP-1-mediated non-homologous end joining of DNA. Arch Biochem Biophys (2016) 606:90–8.10.1016/j.abb.2016.07.014 PubMed DOI
Kameshima H, Yagihashi A, Yajima T, Watanabe N, Ikeda Y. Helicobacter pylori infection induces telomerase activity in premalignant lesions. Am J Gastroenterol (1999) 94(2):547–8.10.1111/j.1572-0241.1999.00547.x PubMed DOI
Chen Z, Cheng Y, Xu Y, Liao J, Zhang X, Hu Y, et al. Expression profiles and function of toll-like receptors 2 and 4 in peripheral blood mononuclear cells of chronic hepatitis B patients. Clin Immunol (2008) 128(3):400–8.10.1016/j.clim.2008.04.006 PubMed DOI
Isogawa M, Robek MD, Furuichi Y, Chisari FV. Toll-like receptor signaling inhibits hepatitis B virus replication in vivo. J Virol (2005) 79(11):7269–72.10.1128/JVI.79.11.7269-7272.2005 PubMed DOI PMC
Tachtatzis PM, Marshall A, Aravinthan A, Verma S, Penrhyn-Lowe S, Mela M, et al. Correction: chronic hepatitis B virus infection: the relation between hepatitis B antigen expression, telomere length, senescence, inflammation and fibrosis. PLoS One (2015) 10(7):e0134315.10.1371/journal.pone.0127511 PubMed DOI PMC
Fan XG, Huang Y, Tang FQ, Yi H. Telomerase activity of peripheral blood lymphocytes in patients with chronic hepatitis B. Immunol Lett (2000) 73(1):7–11.10.1016/S0165-2478(00)00187-5 PubMed DOI
Bailey KL, Romberger DJ, Katafiasz DM, Heires AJ, Sisson JH, Wyatt TA, et al. TLR2 and TLR4 expression and inflammatory cytokines are altered in the airway epithelium of those with alcohol use disorders. Alcohol Clin Exp Res (2015) 39(9):1691–7.10.1111/acer.12803 PubMed DOI PMC
Uesugi T, Froh M, Arteel GE, Bradford BU, Thurman RG. Toll-like receptor 4 is involved in the mechanism of early alcohol-induced liver injury in mice. Hepatology (2001) 34(1):101–8.10.1053/jhep.2001.25350 PubMed DOI
Aida J, Yokoyama A, Izumiyama N, Nakamura K, Ishikawa N, Poon SS, et al. Alcoholics show reduced telomere length in the oesophagus. J Pathol (2011) 223(3):410–6.10.1002/path.2817 PubMed DOI
Pace E, Ferraro M, Siena L, Melis M, Montalbano AM, Johnson M, et al. Cigarette smoke increases toll-like receptor 4 and modifies lipopolysaccharide-mediated responses in airway epithelial cells. Immunology (2008) 124(3):401–11.10.1111/j.1365-2567.2007.02788.x PubMed DOI PMC
Morla M, Busquets X, Pons J, Sauleda J, MacNee W, Agusti AG. Telomere shortening in smokers with and without COPD. Eur Respir J (2006) 27(3):525–8.10.1183/09031936.06.00087005 PubMed DOI
Valdes AM, Andrew T, Gardner JP, Kimura M, Oelsner E, Cherkas LF, et al. Obesity, cigarette smoking, and telomere length in women. Lancet (2005) 366(9486):662–4.10.1016/S0140-6736(05)66630-5 PubMed DOI
Yim HW, Slebos RJ, Randell SH, Umbach DM, Parsons AM, Rivera MP, et al. Smoking is associated with increased telomerase activity in short-term cultures of human bronchial epithelial cells. Cancer Lett (2007) 246(1–2):24–33.10.1016/j.canlet.2006.01.023 PubMed DOI
Poulain-Godefroy O, Le Bacquer O, Plancq P, Lecoeur C, Pattou F, Fruhbeck G, et al. Inflammatory role of toll-like receptors in human and murine adipose tissue. Mediators Inflamm (2010) 2010:823486.10.1155/2010/823486 PubMed DOI PMC
Creely SJ, McTernan PG, Kusminski CM, Fisher FM, Da Silva NF, Khanolkar M, et al. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am J Physiol Endocrinol Metab (2007) 292(3):E740–7.10.1152/ajpendo.00302.2006 PubMed DOI
Metcalf TU, Cubas RA, Ghneim K, Cartwright MJ, Grevenynghe JV, Richner JM, et al. Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors. Aging Cell (2015) 14(3):421–32.10.1111/acel.12320 PubMed DOI PMC
Shaw AC, Goldstein DR, Montgomery RR. Age-dependent dysregulation of innate immunity. Nat Rev Immunol (2013) 13(12):875–87.10.1038/nri3547 PubMed DOI PMC
Nagai Y, Garrett KP, Ohta S, Bahrun U, Kouro T, Akira S, et al. Toll-like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment. Immunity (2006) 24(6):801–12.10.1016/j.immuni.2006.04.008 PubMed DOI PMC
Esplin BL, Shimazu T, Welner RS, Garrett KP, Nie L, Zhang Q, et al. Chronic exposure to a TLR ligand injures hematopoietic stem cells. J Immunol (2011) 186(9):5367–75.10.4049/jimmunol.1003438 PubMed DOI PMC
Baldridge MT, King KY, Boles NC, Weksberg DC, Goodell MA. Quiescent haematopoietic stem cells are activated by IFN-gamma in response to chronic infection. Nature (2010) 465(7299):793–7.10.1038/nature09135 PubMed DOI PMC
Takizawa H, Boettcher S, Manz MG. Demand-adapted regulation of early hematopoiesis in infection and inflammation. Blood (2012) 119(13):2991–3002.10.1182/blood-2011-12-380113 PubMed DOI
Massberg S, Schaerli P, Knezevic-Maramica I, Kollnberger M, Tubo N, Moseman EA, et al. Immunosurveillance by hematopoietic progenitor cells trafficking through blood, lymph, and peripheral tissues. Cell (2007) 131(5):994–1008.10.1016/j.cell.2007.09.047 PubMed DOI PMC
Griseri T, McKenzie BS, Schiering C, Powrie F. Dysregulated hematopoietic stem and progenitor cell activity promotes interleukin-23-driven chronic intestinal inflammation. Immunity (2012) 37(6):1116–29.10.1016/j.immuni.2012.08.025 PubMed DOI PMC
De Luca K, Frances-Duvert V, Asensio MJ, Ihsani R, Debien E, Taillardet M, et al. The TLR1/2 agonist PAM(3)CSK(4) instructs commitment of human hematopoietic stem cells to a myeloid cell fate. Leukemia (2009) 23(11):2063–74.10.1038/leu.2009.155 PubMed DOI
Zhao Y, Ling F, Wang HC, Sun XH. Chronic TLR signaling impairs the long-term repopulating potential of hematopoietic stem cells of wild type but not Id1 deficient mice. PLoS One (2013) 8(2):e55552.10.1371/journal.pone.0055552 PubMed DOI PMC
Akala OO, Clarke MF. Hematopoietic stem cell self-renewal. Curr Opin Genet Dev (2006) 16(5):496–501.10.1016/j.gde.2006.08.011 PubMed DOI
Orford K, Scadden D. Deconstructing stem cell self-renewal: genetic insights into cell-cycle regulation. Nat Rev Genet (2008) 9(2):115–28.10.1038/nrg2269 PubMed DOI
Boiko JR, Borghesi L. Hematopoiesis sculpted by pathogens: toll-like receptors and inflammatory mediators directly activate stem cells. Cytokine (2012) 57(1):1–8.10.1016/j.cyto.2011.10.005 PubMed DOI PMC
Serbina NV, Hohl TM, Cherny M, Pamer EG. Selective expansion of the monocytic lineage directed by bacterial infection. J Immunol (2009) 183(3):1900–10.10.4049/jimmunol.0900612 PubMed DOI PMC
Takizawa H, Regoes RR, Boddupalli CS, Bonhoeffer S, Manz MG. Dynamic variation in cycling of hematopoietic stem cells in steady state and inflammation. J Exp Med (2011) 208(2):273–84.10.1084/jem.20101643 PubMed DOI PMC
Megias J, Maneu V, Salvador P, Gozalbo D, Gil ML. Candida albicans stimulates in vivo differentiation of haematopoietic stem and progenitor cells towards macrophages by a TLR2-dependent signalling. Cell Microbiol (2013) 15(7):1143–53.10.1111/cmi.12104 PubMed DOI
Schmid MA, Takizawa H, Baumjohann DR, Saito Y, Manz MG. Bone marrow dendritic cell progenitors sense pathogens via toll-like receptors and subsequently migrate to inflamed lymph nodes. Blood (2011) 118(18):4829–40.10.1182/blood-2011-03-344960 PubMed DOI
Ziegler P, Boettcher S, Takizawa H, Manz MG, Brummendorf TH. LPS-stimulated human bone marrow stroma cells support myeloid cell development and progenitor cell maintenance. Ann Hematol (2016) 95(2):173–8.10.1007/s00277-015-2550-5 PubMed DOI
Boettcher S, Ziegler P, Schmid MA, Takizawa H, van Rooijen N, Kopf M, et al. Cutting edge: LPS-induced emergency myelopoiesis depends on TLR4-expressing nonhematopoietic cells. J Immunol (2012) 188(12):5824–8.10.4049/jimmunol.1103253 PubMed DOI
Bugl S, Wirths S, Radsak MP, Schild H, Stein P, Andre MC, et al. Steady-state neutrophil homeostasis is dependent on TLR4/TRIF signaling. Blood (2013) 121(5):723–33.10.1182/blood-2012-05-429589 PubMed DOI
Colla S, Ong DS, Ogoti Y, Marchesini M, Mistry NA, Clise-Dwyer K, et al. Telomere dysfunction drives aberrant hematopoietic differentiation and myelodysplastic syndrome. Cancer Cell (2015) 27(5):644–57.10.1016/j.ccell.2015.04.007 PubMed DOI PMC
Al-Ajmi N, Saretzki G, Miles C, Spyridopoulos I. Dietary restriction ameliorates haematopoietic ageing independent of telomerase, whilst lack of telomerase and short telomeres exacerbates the ageing phenotype. Exp Gerontol (2014) 58:113–9.10.1016/j.exger.2014.07.010 PubMed DOI
Rossi DJ, Bryder D, Seita J, Nussenzweig A, Hoeijmakers J, Weissman IL. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature (2007) 447(7145):725–9.10.1038/nature05862 PubMed DOI
Chambers SM, Shaw CA, Gatza C, Fisk CJ, Donehower LA, Goodell MA. Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation. PLoS Biol (2007) 5(8):e201.10.1371/journal.pbio.0050201 PubMed DOI PMC
Bhattacharjee RN, Banerjee B, Akira S, Hande MP. Telomere-mediated chromosomal instability triggers TLR4 induced inflammation and death in mice. PLoS One (2010) 5(7):e11873.10.1371/journal.pone.0011873 PubMed DOI PMC
Harberts E, Gaspari AA. TLR signaling and DNA repair: are they associated? J Invest Dermatol (2013) 133(2):296–302.10.1038/jid.2012.288 PubMed DOI PMC
Liang Y, Van Zant G, Szilvassy SJ. Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells. Blood (2005) 106(4):1479–87.10.1182/blood-2004-11-4282 PubMed DOI PMC
Robbins CS, Chudnovskiy A, Rauch PJ, Figueiredo JL, Iwamoto Y, Gorbatov R, et al. Extramedullary hematopoiesis generates Ly-6C(high) monocytes that infiltrate atherosclerotic lesions. Circulation (2012) 125(2):364–74.10.1161/CIRCULATIONAHA.111.061986 PubMed DOI PMC
Murakami S, Yamamoto M, Motohashi H. Hematopoietic stem and progenitor cell activation during chronic dermatitis provoked by constitutively active aryl-hydrocarbon receptor driven by keratin 14 promoter. Toxicol Sci (2014) 138(1):47–58.10.1093/toxsci/kft273 PubMed DOI
McGettrick AF, O’Neill LA. Toll-like receptors: key activators of leucocytes and regulator of haematopoiesis. Br J Haematol (2007) 139(2):185–93.10.1111/j.1365-2141.2007.06802.x PubMed DOI
Zhang H, Rodriguez S, Wang L, Wang S, Serezani H, Kapur R, et al. Sepsis induces hematopoietic stem cell exhaustion and myelosuppression through distinct contributions of TRIF and MYD88. Stem Cell Reports (2016) 6(6):940–56.10.1016/j.stemcr.2016.05.002 PubMed DOI PMC
Shaw PJ, Kan F, Woo Ahn K, Spellman SR, Aljurf M, Ayas M, et al. Outcomes of pediatric bone marrow transplantation for leukemia and myelodysplasia using matched sibling, mismatched related, or matched unrelated donors. Blood (2010) 116(19):4007–15.10.1182/blood-2010-01-261958 PubMed DOI PMC
Kauppila TE, Kauppila JH, Larsson NG. Mammalian mitochondria and aging: an update. Cell Metab (2017) 25(1):57–71.10.1016/j.cmet.2016.09.017 PubMed DOI
Li N, Ragheb K, Lawler G, Sturgis J, Rajwa B, Melendez JA, et al. Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. J Biol Chem (2003) 278(10):8516–25.10.1074/jbc.M210432200 PubMed DOI
Shimada K, Crother TR, Karlin J, Dagvadorj J, Chiba N, Chen S, et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity (2012) 36(3):401–14.10.1016/j.immuni.2012.01.009 PubMed DOI PMC
Passos JF, Saretzki G, Ahmed S, Nelson G, Richter T, Peters H, et al. Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence. PLoS Biol (2007) 5(5):e110.10.1371/journal.pbio.0050110 PubMed DOI PMC
Handa H, Matsushima T, Nishimoto N, Inoue M, Saitoh T, Yokohama A, et al. Flow cytometric detection of human telomerase reverse transcriptase (hTERT) expression in a subpopulation of bone marrow cells. Leuk Res (2010) 34(2):177–83.10.1016/j.leukres.2009.06.010 PubMed DOI
Narducci ML, Grasselli A, Biasucci LM, Farsetti A, Mule A, Liuzzo G, et al. High telomerase activity in neutrophils from unstable coronary plaques. J Am Coll Cardiol (2007) 50(25):2369–74.10.1016/j.jacc.2007.08.048 PubMed DOI
Lepreux S, Doudnikoff E, Aubert I, Bioulac-Sage P, Bloch B, Martin-Negrier ML. Cytoplasmic expression of human telomerase catalytic protein (hTERT) in neutrophils: an immunoelectron microscopy study. Ultrastruct Pathol (2008) 32(5):178–83.10.1080/01913120802034504 PubMed DOI
Kim YW, Byzova TV. Oxidative stress in angiogenesis and vascular disease. Blood (2014) 123(5):625–31.10.1182/blood-2013-09-512749 PubMed DOI PMC
Xie Z, Jay KA, Smith DL, Zhang Y, Liu Z, Zheng J, et al. Early telomerase inactivation accelerates aging independently of telomere length. Cell (2015) 160(5):928–39.10.1016/j.cell.2015.02.002 PubMed DOI PMC
da Silva MS, Segatto M, Pavani RS, Gutierrez-Rodrigues F, Bispo VD, de Medeiros MH, et al. Consequences of acute oxidative stress in Leishmania amazonensis: from telomere shortening to the selection of the fittest parasites. Biochim Biophys Acta (2017) 1864(1):138–50.10.1016/j.bbamcr.2016.11.001 PubMed DOI
Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature (1990) 345(6274):458–60.10.1038/345458a0 PubMed DOI
Indran IR, Hande MP, Pervaiz S. hTERT overexpression alleviates intracellular ROS production, improves mitochondrial function, and inhibits ROS-mediated apoptosis in cancer cells. Cancer Res (2011) 71(1):266–76.10.1158/0008-5472.CAN-10-1588 PubMed DOI
Nitta E, Yamashita M, Hosokawa K, Xian M, Takubo K, Arai F, et al. Telomerase reverse transcriptase protects ATM-deficient hematopoietic stem cells from ROS-induced apoptosis through a telomere-independent mechanism. Blood (2011) 117(16):4169–80.10.1182/blood-2010-08-297390 PubMed DOI
Gursel I, Gursel M, Yamada H, Ishii KJ, Takeshita F, Klinman DM. Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation. J Immunol (2003) 171(3):1393–400.10.4049/jimmunol.171.3.1393 PubMed DOI
Yin L, Hubbard AK, Giardina C. NF-kappa B regulates transcription of the mouse telomerase catalytic subunit. J Biol Chem (2000) 275(47):36671–5.10.1074/jbc.M007378200 PubMed DOI
Xu D, Erickson S, Szeps M, Gruber A, Sangfelt O, Einhorn S, et al. Interferon alpha down-regulates telomerase reverse transcriptase and telomerase activity in human malignant and nonmalignant hematopoietic cells. Blood (2000) 96(13):4313–8. PubMed
Ghosh A, Saginc G, Leow SC, Khattar E, Shin EM, Yan TD, et al. Telomerase directly regulates NF-kappaB-dependent transcription. Nat Cell Biol (2012) 14(12):1270–81.10.1038/ncb2621 PubMed DOI
Hoffmeyer K, Raggioli A, Rudloff S, Anton R, Hierholzer A, Del Valle I, et al. Wnt/beta-catenin signaling regulates telomerase in stem cells and cancer cells. Science (2012) 336(6088):1549–54.10.1126/science.1218370 PubMed DOI
Wu XQ, Yang Y, Li WX, Cheng YH, Li XF, Huang C, et al. Telomerase reverse transcriptase acts in a feedback loop with NF-kappaB pathway to regulate macrophage polarization in alcoholic liver disease. Sci Rep (2016) 6:18685.10.1038/srep18685 PubMed DOI PMC
Rentoukas E, Tsarouhas K, Kaplanis I, Korou E, Nikolaou M, Marathonitis G, et al. Connection between telomerase activity in PBMC and markers of inflammation and endothelial dysfunction in patients with metabolic syndrome. PLoS One (2012) 7(4):e35739.10.1371/journal.pone.0035739 PubMed DOI PMC
Deelen J, Beekman M, Codd V, Trompet S, Broer L, Hagg S, et al. Leukocyte telomere length associates with prospective mortality independent of immune-related parameters and known genetic markers. Int J Epidemiol (2014) 43(3):878–86.10.1093/ije/dyt267 PubMed DOI PMC
Calado RT, Dumitriu B. Telomere dynamics in mice and humans. Semin Hematol (2013) 50(2):165–74.10.1053/j.seminhematol.2013.03.030 PubMed DOI PMC