Proinflammatory profile of in vitro monocytes in the ageing is affected by lymphocytes presence

Immunity & Ageing

Vanessa Soares Lara²  James Venturini¹  Magda Paula Pereira do Nascimento²  Patricia Freitas Faria²  Bruno Calzavara²  Karen Henriette Pinke² 

[1] Laboratory of Experimental Immunology, Department of Biological Sciences, Faculty of Science, São Paulo State University, Av Eng Luiz Edmundo C, 14-01, 17033-360, Bauru, SP, Brazil;Department of Stomatology, Bauru School of Dentistry, University of São Paulo, Al. Dr. Octávio Pinheiro Brisola, 9-75, 17012-901, Bauru, SP, Brazil

关键词: Inflamm-aging;    Cytokines;    PBMC;    Monocytes;    Immunosenescence;   

Others  :  814995
DOI  :  10.1186/1742-4933-10-22

 received in 2012-09-14, accepted in 2013-06-02,  发布年份 2013

【 摘 要 】

Background

Aging is associated with complex and constant remodeling of the immune function, resulting in an increasing susceptibility to infection and others diseases. The infections caused by Gram-negative microorganisms, present in nursing homes and hospitals, constitute one of the most common infections in the elderly, and are mainly combated by innate immune cells. Although the functions of innate immunity seem more preserved during aging than of adaptive immune mechanisms, two systems operate in an integrated way in the body, so that injury in one part of the immune system inevitably affects the other as they are part of a defensive network. The aim of this study was to investigate the in vitro production of proinflammatory (TNF-α, IL-6, IL-1β, CXCL-8 and MCP-1) and anti-inflammatory (TGF-β and IL-10) cytokines by monocytes, stimulated or not (basal) with lipopolysaccharide, from healthy young and elderly subjects. By means of PBMCs, we also studied if cytokine profile is altered in these different patient groups, in the presence of lymphocytes, under the same experimental conditions.

Results

The monocytes from elderly presented higher basal production of TNF-α, MCP-1 and lower of TGF-β than young monocytes. PBMC showed similar cytokines production, irrespective age or stimulation presence. In the presence of lymphocytes, the spontaneous production of IL-10 was higher and of TGF-β was lower than monocytes, regardless of age. After LPS-stimulation, the presence of lymphocytes resulted in increased IL-6, IL-1β, MCP-1 and IL-10 and decreased CXCL-8 and TGF-β in comparison to pure culture of monocytes from young patients. With age, the same differences were observed, except for CXCL-8 and TGF-β which production was the same between monocytes and PBMC stimulated with LPS.

Conclusion

These findings reinforce the systemic state of inflamm-aging frequently reported in elderly and considered a factor of susceptibility to numerous diseases. Still, the cytokine production from just monocytes of the elderly showed alterations, while in the lymphocyte presence not, suggesting an immunomodulator role of lymphocytes on monocytes. In addition, the differences between the production patterns by LPS-stimulated PBMC between young and elderly volunteers can be related with an imbalance in response against Gram-negative bacteria in throughout life.

【 授权许可】

   
2013 Pinke et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Ongradi J, Kovesdi V: Factors that may impact on immunosenescence: an appraisal. Immunity & ageing: I & A 2010, 7:7. BioMed Central Full Text
• [2]Della Bella S, Bierti L, Presicce P, Arienti R, Valenti M, Saresella M, Vergani C, Villa ML: Peripheral blood dendritic cells and monocytes are differently regulated in the elderly. Clin Immunol 2007, 122:220-228.
• [3]Gruver AL, Hudson LL, Sempowski GD: Immunosenescence of ageing. J Pathol 2007, 211:144-156.
• [4]Pawelec G, Larbi A: Immunity and ageing in man: Annual Review 2006/2007. Exp Gerontol 2008, 43:34-38.
• [5]Gasparoto TH, Vieira NA, Porto VC, Campanelli AP, Lara VS: Ageing exacerbates damage of systemic and salivary neutrophils from patients presenting Candida-related denture stomatitis. Immunity & ageing: I & A 2009, 6:3. BioMed Central Full Text
• [6]Gasparoto TH, Vieira NA, Porto VC, Campanelli AP, Lara VS: Differences between salivary and blood neutrophils from elderly and young denture wearers. J Oral Rehabil 2011, 38:41-51.
• [7]Gasparoto TH, de Oliveira CE, Vieira NA, Porto VC, Cunha FQ, Garlet GP, Campanelli AP, Lara VS: Activation pattern of neutrophils from blood of elderly individuals with Candida-related denture stomatitis. Eur J Clin Microbiol Infect Dis 2012, 31:1271-1277.
• [8]Weiskopf D, Weinberger B, Grubeck-Loebenstein B: The aging of the immune system. Transplant international: official journal of the European Society for Organ Transplantation 2009, 22:1041-1050.
• [9]Ciaramella A, Spalletta G, Bizzoni F, Salani F, Caltagirone C, Bossu P: Effect of age on surface molecules and cytokine expression in human dendritic cells. Cell Immunol 2011, 269:82-89.
• [10]Malaguarnera L, Ferlito L, Imbesi RM, Gulizia GS, Di Mauro S, Maugeri D, Malaguarnera M, Messina A: Immunosenescence: a review. Arch Gerontol Geriatr 2001, 32:1-14.
• [11]Rubin H: Promise and problems in relating cellular senescence in vitro to aging in vivo. Arch Gerontol Geriatr 2002, 34:275-286.
• [12]Batory G, Beregi E, Petranyi GG: Lymphocyte subpopulation changes by aging. Arch Gerontol Geriatr 1982, 1:129-142.
• [13]Motta M, Ferlito L, Malaguarnera L, Vinci E, Bosco S, Maugeri D, Malaguarnera M: Alterations of the lymphocytic set-up in elderly patients with cancer. Arch Gerontol Geriatr 2003, 36:7-14.
• [14]Agarwal S, Busse PJ: Innate and adaptive immunosenescence. Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 2010, 104:183-190. quiz 190–182, 210
• [15]Schneider EL: Infectious diseases in the elderly. Ann Intern Med 1983, 98:395-400.
• [16]Crossley KB, Peterson PK: Infections in the elderly. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 1996, 22:209-215.
• [17]Sansoni P, Vescovini R, Fagnoni F, Biasini C, Zanni F, Zanlari L, Telera A, Lucchini G, Passeri G, Monti D, et al.: The immune system in extreme longevity. Exp Gerontol 2008, 43:61-65.
• [18]Panda A, Arjona A, Sapey E, Bai F, Fikrig E, Montgomery RR, Lord JM, Shaw AC: Human innate immunosenescence: causes and consequences for immunity in old age. Trends Immunol 2009, 30:325-333.
• [19]Alper S: Model systems to the rescue: The relationship between aging and innate immunity. Communicative & integrative biology 2010, 3:409-414.
• [20]Shaw AC, Joshi S, Greenwood H, Panda A, Lord JM: Aging of the innate immune system. Curr Opin Immunol 2010, 22:507-513.
• [21]Gordon S, Taylor PR: Monocyte and macrophage heterogeneity. Nat Rev Immunol 2005, 5:953-964.
• [22]Guha M, Mackman N: LPS induction of gene expression in human monocytes. Cell Signal 2001, 13:85-94.
• [23]Mozes T, Barath I, Gornicsar K, Grosz A, Mozes T, Gondocs C, Szephalmi P, Gaal K, Madarasz E: Deviations in circulating TNFalpha levels and TNFalpha production by mononuclear cells in healthy human populations. Mediators Inflamm 2011, 2011:972609.
• [24]Schroecksnadel K, Frick B, Winkler C, Fuchs D: Crucial role of interferon-gamma and stimulated macrophages in cardiovascular disease. Curr Vasc Pharmacol 2006, 4:205-213.
• [25]Smith JK, Dykes R, Douglas JE, Krishnaswamy G, Berk S: Long-term exercise and atherogenic activity of blood mononuclear cells in persons at risk of developing ischemic heart disease. JAMA 1999, 281:1722-1727.
• [26]Chomarat P, Rissoan MC, Banchereau J, Miossec P: Interferon gamma inhibits interleukin 10 production by monocytes. J Exp Med 1993, 177:523-527.
• [27]Xiong J, Kang K, Liu L, Yoshida Y, Cooper KD, Ghannoum MA: Candida albicans and Candida krusei differentially induce human blood mononuclear cell interleukin-12 and gamma interferon production. Infect Immun 2000, 68:2464-2469.
• [28]Seitz M, Deimann W, Gram N, Hunstein W, Gemsa D: Characterization of blood mononuclear cells of rheumatoid arthritis patients. I. Depressed lymphocyte proliferation and enhanced prostanoid release from monocytes. Clinical immunology and immunopathology 1982, 25:405-416.
• [29]Netea MG, Gijzen K, Coolen N, Verschueren I, Figdor C, Van der Meer JW, Torensma R, Kullberg BJ: Human dendritic cells are less potent at killing Candida albicans than both monocytes and macrophages. Microbes and infection / Institut Pasteur 2004, 6:985-989.
• [30]Netea MG, Sutmuller R, Hermann C, Van der Graaf CA, Van der Meer JW, van Krieken JH, Hartung T, Adema G, Kullberg BJ: Toll-like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cells. J Immunol 2004, 172:3712-3718.
• [31]Hirokawa K: Age-related changes of signal transduction in T cells. Exp Gerontol 1999, 34:7-18.
• [32]Linton PJ, Dorshkind K: Age-related changes in lymphocyte development and function. Nat Immunol 2004, 5:133-139.
• [33]McLachlan JA, Serkin CD, Morrey-Clark KM, Bakouche O: Immunological functions of aged human monocytes. Pathobiology: journal of immunopathology, molecular and cellular biology 1995, 63:148-159.
• [34]Nyugen J, Agrawal S, Gollapudi S, Gupta S: Impaired functions of peripheral blood monocyte subpopulations in aged humans. J Clin Immunol 2010, 30:806-813.
• [35]Fulop T, Larbi A, Kotb R, de Angelis F, Pawelec G: Aging, immunity, and cancer. Discov Med 2011, 11:537-550.
• [36]Aw D, Silva AB, Palmer DB: Immunosenescence: emerging challenges for an ageing population. Immunology 2007, 120:435-446.
• [37]Paolisso G, Rizzo MR, Mazziotti G, Tagliamonte MR, Gambardella A, Rotondi M, Carella C, Giugliano D, Varricchio M, D'Onofrio F: Advancing age and insulin resistance: role of plasma tumor necrosis factor-alpha. Am J Physiol 1998, 275:E294-E299.
• [38]Bruunsgaard H, Andersen-Ranberg K, Jeune B, Pedersen AN, Skinhoj P, Pedersen BK: A high plasma concentration of TNF-alpha is associated with dementia in centenarians. The journals of gerontology Series A, Biological sciences and medical sciences 1999, 54:M357-M364.
• [39]Aggarwal BB: Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol 2003, 3:745-756.
• [40]Vasto S, Candore G, Balistreri CR, Caruso M, Colonna-Romano G, Grimaldi MP, Listi F, Nuzzo D, Lio D, Caruso C: Inflammatory networks in ageing, age-related diseases and longevity. Mech Ageing Dev 2007, 128:83-91.
• [41]Carr MW, Roth SJ, Luther E, Rose SS, Springer TA: Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant. Proc Natl Acad Sci U S A 1994, 91:3652-3656.
• [42]Jiang Y, Russell TR, Graves DT, Cheng H, Nong SH, Levitz SM: Monocyte chemoattractant protein 1 and interleukin-8 production in mononuclear cells stimulated by oral microorganisms. Infect Immun 1996, 64:4450-4455.
• [43]Tsou CL, Peters W, Si Y, Slaymaker S, Aslanian AM, Weisberg SP, Mack M, Charo IF: Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites. J Clin Invest 2007, 117:902-909.
• [44]Jia T, Serbina NV, Brandl K, Zhong MX, Leiner IM, Charo IF, Pamer EG: Additive roles for MCP-1 and MCP-3 in CCR2-mediated recruitment of inflammatory monocytes during Listeria monocytogenes infection. J Immunol 2008, 180:6846-6853.
• [45]Yadav A, Saini V, Arora S: MCP-1: chemoattractant with a role beyond immunity: a review. Clinica chimica acta; international journal of clinical chemistry 2010, 411:1570-1579.
• [46]Mansfield AS, Nevala WK, Dronca RS, Leontovich AA, Shuster L, Markovic SN: Normal ageing is associated with an increase in Th2 cells, MCP-1 (CCL1) and RANTES (CCL5), with differences in sCD40L and PDGF-AA between sexes. Clin Exp Immunol 2012, 170:186-193.
• [47]Song Y, Shen H, Schenten D, Shan P, Lee PJ, Goldstein DR: Aging enhances the basal production of IL-6 and CCL2 in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 2012, 32:103-109.
• [48]Jackaman C, Radley-Crabb HG, Soffe Z, Shavlakadze T, Grounds MD, Nelson DJ: Targeting macrophages rescues age-related immune deficiencies in C57BL/6J geriatric mice. Aging Cell 2013, 12:345-357.
• [49]Doyle KP, Cekanaviciute E, Mamer LE, Buckwalter MS: TGFbeta signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke. J Neuroinflammation 2010, 7:62. BioMed Central Full Text
• [50]Li MO, Wan YY, Sanjabi S, Robertson AK, Flavell RA: Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol 2006, 24:99-146.
• [51]Roilides E, Anastasiou-Katsiardani A, Dimitriadou-Georgiadou A, Kadiltsoglou I, Tsaparidou S, Panteliadis C, Walsh TJ: Suppressive effects of interleukin-10 on human mononuclear phagocyte function against Candida albicans and Staphylococcus aureus. J Infect Dis 1998, 178:1734-1742.
• [52]Baltch AL, Smith RP, Franke MA, Ritz WJ, Michelsen PB, Bopp LH: Effects of cytokines and fluconazole on the activity of human monocytes against Candida albicans. Antimicrob Agents Chemother 2001, 45:96-104.
• [53]Dongari-Bagtzoglou A, Fidel PL Jr: The host cytokine responses and protective immunity in oropharyngeal candidiasis. J Dent Res 2005, 84:966-977.
• [54]Wahl SM, Hunt DA, Wakefield LM, McCartney-Francis N, Wahl LM, Roberts AB, Sporn MB: Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci USA 1987, 84:5788-5792.
• [55]De Martinis M, Franceschi C, Monti D, Ginaldi L: Inflamm-ageing and lifelong antigenic load as major determinants of ageing rate and longevity. FEBS Lett 2005, 579:2035-2039.
• [56]Ginaldi L, Di Benedetto MC, De Martinis M: Osteoporosis, inflammation and ageing. Immunity & ageing: I & A 2005, 2:14. BioMed Central Full Text
• [57]Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G: Inflamm-aging. An evolutionary perspective on immunosenescence. Annals of the New York Academy of Sciences 2000, 908:244-254.
• [58]Kaplin A, Carroll KA, Cheng J, Allie R, Lyketsos CG, Calabresi P, Rosenberg PB: IL-6 release by LPS-stimulated peripheral blood mononuclear cells as a potential biomarker in Alzheimer's disease. International psychogeriatrics / IPA 2009, 21:413-414.
• [59]Liuzzo G, Angiolillo DJ, Buffon A, Rizzello V, Colizzi C, Ginnetti F, Biasucci LM, Maseri A: Enhanced response of blood monocytes to in vitro lipopolysaccharide-challenge in patients with recurrent unstable angina. Circulation 2001, 103:2236-2241.
• [60]Riancho JA, Zarrabeitia MT, Amado JA, Olmos JM, Gonzalez-Macias J: Age-related differences in cytokine secretion. Gerontology 1994, 40:8-12.
• [61]Candore G, Caruso C, Colonna-Romano G: Inflammation, genetic background and longevity. Biogerontology 2010, 11:565-573.
• [62]Zanni F, Vescovini R, Biasini C, Fagnoni F, Zanlari L, Telera A, Di Pede P, Passeri G, Pedrazzoni M, Passeri M, et al.: Marked increase with age of type 1 cytokines within memory and effector/cytotoxic CD8+ T cells in humans: a contribution to understand the relationship between inflammation and immunosenescence. Exp Gerontol 2003, 38:981-987.
• [63]Gerli R, Monti D, Bistoni O, Mazzone AM, Peri G, Cossarizza A, Di Gioacchino M, Cesarotti ME, Doni A, Mantovani A, et al.: Chemokines, sTNF-Rs and sCD30 serum levels in healthy aged people and centenarians. Mech Ageing Dev 2000, 121:37-46.
• [64]Gon Y, Hashimoto S, Hayashi S, Koura T, Matsumoto K, Horie T: Lower serum concentrations of cytokines in elderly patients with pneumonia and the impaired production of cytokines by peripheral blood monocytes in the elderly. Clin Exp Immunol 1996, 106:120-126.
• [65]Bruunsgaard H, Pedersen AN, Schroll M, Skinhoj P, Pedersen BK: Impaired production of proinflammatory cytokines in response to lipopolysaccharide (LPS) stimulation in elderly humans. Clin Exp Immunol 1999, 118:235-241.
• [66]Sadeghi HM, Schnelle JF, Thoma JK, Nishanian P, Fahey JL: Phenotypic and functional characteristics of circulating monocytes of elderly persons. Exp Gerontol 1999, 34:959-970.
• [67]Stockinger B, Veldhoen M, Martin B: Th17 T cells: linking innate and adaptive immunity. Semin Immunol 2007, 19:353-361.
• [68]Goronzy JJ, Lee WW, Weyand CM: Aging and T-cell diversity. Exp Gerontol 2007, 42:400-406.
• [69]Njemini R, Lambert M, Demanet C, Mets T: The effect of aging and inflammation on heat shock protein 27 in human monocytes and lymphocytes. Exp Gerontol 2006, 41:312-319.
• [70]Wenisch C, Patruta S, Daxbock F, Krause R, Horl W: Effect of age on human neutrophil function. J Leukoc Biol 2000, 67:40-45.