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Exp Clin Endocrinol Diabetes 2008; 116(3): 162-166
DOI: 10.1055/s-2007-990278
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Reduced Frequency of Peripheral Dendritic Cells in Type 2 Diabetes

C. C. Seifarth 1 , C. Hinkmann 1 , E.-G. Hahn 1 , T. Lohmann 2 , I. A. Harsch 1
  • 1Medizinische Klinik 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
  • 2Medizinische Klinik, Städtisches Krankenhaus Dresden-Neustadt, Dresden, Germany
Further Information

Publication History

received 20.05.2007 first decision 06.07.2007

accepted 02.08.2007

Publication Date:
23 January 2008 (online)

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Abstract

Objective: It is a common clinical experience that type 2 diabetic patients are susceptible to opportunistic infections. The underlying reasons for this immune deficiency are not yet understood. Dendritic cells (DC) play a key role in initiating innate and adapted immune responses.

Design: In order to investigate changes in the DC compartment in the peripheral blood in type 2 diabetes, we analyzed blood from patients under poor and good metabolic control and compared them to healthy controls.

Patients: 5 mls of blood were collected from 15 healthy controls, 15 diabetic patients with an HbA1c <7.0 and 15 patients with an HbA1c >9.5%. Age range was 44-80 years. Patients were age-matched with the control group.

Measurement: Blood DC were enumerated by flow cytometry after staining with antibodies against the blood dendritic cells antigens 1-3 (BDCA 1-3). This allows quantification of the DC subtypes: myeloid dendritic cells type 1 (mDC1, mDC2) and plasmacytoid dendritic cells (pDC).

Results: The relative and absolute frequency for both mDC1 and pDC was clearly diminished in patients with poor metabolic control as compared to healthy controls. In patients with good metabolic control the reduction of DC was less pronounced but still significant, particularly for mDC1.

Conclusion: Hyperglycemic metabolism does affect the pool of peripheral DCs and leads to a reduction of both, mDC1 and pDC. Even patients considered to be under good metabolic control appear to have a reduced peripheral pool of DC.

Key words

type 2 diabetes - dendritic cells - immune deficiency

References

  • 1 Müller LM, Gorter KJ, Hak E, Goudzwaard WL, Schellevis FG, Hoepelman AI, Rutten GE. Increased risk of common infections in patients with type 1 and type 2 diabetes mellitus.  Clin Infect Dis. 2005;  41 281-288
    CrossrefPubMedGoogle Scholar
  • 2 Shah BR, Hux JE. Quantifying the risk of infectious diseases for people with diabetes.  Diab Care. 2003;  26 510-513
    CrossrefPubMedGoogle Scholar
  • 3 Balasoiu D, Kessel KC van, Kats-Renaud HJ van, Collet TJ, Hoepelman AI. Granulocyte function in women with diabetes and asymptomatic bacteriuria.  Diab Care. 1997;  20 392-395
    CrossrefPubMedGoogle Scholar
  • 4 Patterson JE, Andriole VT. Bacterial urinary tract infections in diabetes.  Infect Dis Clin North Am. 1997;  11 735-750
    CrossrefPubMedGoogle Scholar
  • 5 Joshi N, Caputo GM, Weitekamp MR, Karchmer AW. Infections in patients with diabetes mellitus.  N Engl J Med. 1999;  341 1906-1912
    CrossrefPubMedGoogle Scholar
  • 6 Boyko EJ, Lipsky BA. Infection and diabetes. In Harris MI, Cowie CC, Stern MP, Boyko EJ, Reiber GE, Bennet PH, Eds. Diabetes in America. 2nd ed. Bethesda, MD, National Institute of Health 1995: 485-499
    Google Scholar
  • 7 Koziel H, Koziel MJ. Pulmonary complications of diabetes mellitus.  Pneumonia. Infect Dis Clin North Am. 1995;  9 65-69
    PubMedGoogle Scholar
  • 8 Calvet HM, Yoshikawa TT. Infections in diabetes.  Infect Dis Clin North Am. 2001;  15 407-421
    CrossrefPubMedGoogle Scholar
  • 9 Pozzilli P, Leslie RD. Infections and diabetes: mechanisms and prospects for prevention.  Diab Med. 1994;  11 935-941
    PubMedGoogle Scholar
  • 10 Delamaire M, Maugendre D, Moreno M, Goff MC Le, Allannic H, Genetet B. Impaired leucocyte functions in diabetic patients.  Diab Med. 1997;  14 29-34
    CrossrefPubMedGoogle Scholar
  • 11 Gallacher SJ, Thomson G, Fraser WD, Fisher BM, Gemmell CG, MacCuish AC. Neutrophil bactericidal function in diabetes mellitus: evidence for association with blood glucose control.  Diab Med. 1995;  12 916-920
    PubMedGoogle Scholar
  • 12 Arafat HA, Lada E, Katakam AK, Amin N. Osteopontin deficiency impacts the pancreatic TH1/TH2 cytokine profile following multiple low dose streptozotocin-induced diabetes.  Exp Clin Endocrinol Diabetes. 2006;  114 555-562
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Mostafazadeh A, Herder C, Haastert B, Hanifi-Moghaddam P, Schloot N, Koenig W, Illig T, Thorand B, Holle R, Eslami MB, Kolb H. KORA Group . Association of humoral immunity to human Hsp60 with the IL-6 gene polymorphism C-174G in patients with type 2 diabetes and controls.  Horm Metab Res. 2005;  37 257-263
    PubMedGoogle Scholar
  • 14 Granucci F, Foti M, Ricciardi-Castagnoli P. Dendritic cell biology.  Adv Immun. 2005;  88 193-233
    PubMedGoogle Scholar
  • 15 Zhang Z, Wang FS. Plasmacytoid dendritic cells act as the most competent cell type in linking antiviral innate and adaptive immune responses.  Cell Mol Immun. 2005;  2 411-417
    PubMedGoogle Scholar
  • 16 Rossi M, Young JW. Human dendritic cells: potent antigen-presenting cells at the crossroads of innate and adaptive immunity.  J Immun. 2005;  175 1373-1381
    PubMedGoogle Scholar
  • 17 Takahashi K, Honeyman MC, Harrison LC. Impaired yield, phenotype, and function of monocyte-derived dendritic cells in humans at risk for insulin-dependent diabetes.  J Immun. 1998;  161 2629-2635
    PubMedGoogle Scholar
  • 18 Poligone B, Weaver Jr DJ, Sen P, Baldwin Jr AS, Tisch R. Elevated NF-kappaB activation in nonobese diabetic mouse dendritic cells results in enhanced APC function.  J Immunol. 2002;  168 188-196
    PubMedGoogle Scholar
  • 19 Weaver Jr DJ, Poligone B, Bui T, Abdel-Motal UM, Baldwin Jr AS, Tisch R. Dendritic cells from nonobese diabetic mice exhibit a defect in NF-kappa B regulation due to a hyperactive I kappa B kinase.  J Immunol. 2001;  167 1461-1468
    PubMedGoogle Scholar
  • 20 Morin J, Chimenes A, Boitard C, Berthier R, Boudaly S. Granulocyte-dendritic cell unbalance in the non-obese diabetic mice.  Cell Immun. 2003;  223 13-25
    CrossrefPubMedGoogle Scholar
  • 21 Spatz M, Eibl N, Hink S, Wolf HM, Fischer GF, Mayr WR, Schernthaner G, Eibl MM. Impaired primary immune response in type-1 diabetes. Functional impairment at the level of APCs and T-cells.  Cell Immun. 2003;  221 5-26
    PubMedGoogle Scholar
  • 22 MacDonald KP, Munster DJ, Clark GJ, Dzionek A, Schmitz J, Hart DN. Characterization of human blood dendritic cell subsets.  Blood. 2002;  100 4512-4520
    CrossrefPubMedGoogle Scholar
  • 23 Dzionek A, Fuchs A, Schmidt P, Cremer S, Zysk M, Miltenyi S, Buck DW, Schmitz J. BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood.  J Immunol. 2001;  65 6037-6046
    PubMedGoogle Scholar
  • 24 Robinson SP, Patterson S, English N, Davies D, Knight SC, Reid CD. Human peripheral blood contains two distinct lineages of dendritic cells.  Eur J Immun. 1999;  29 2769-2778
    PubMedGoogle Scholar
  • 25 Rissoan MC, Soumelis V, Kadowaki N, Grouard G, Briere F, Waal Malefyt R de, Liu YJ. Reciprocal control of T helper cell and dendritic cell differentiation.  Science. 1999;  283 1183-1186
    CrossrefPubMedGoogle Scholar
  • 26 Penna G, Vulcano M, Sozzani S, Adorini L. Differential migration behavior and chemokine production by myeloid and plasmacytoid dendritic cells.  Hum Immunol. 2002;  63 1164-1171
    CrossrefPubMedGoogle Scholar
  • 27 Jonuleit H, Schmitt E, Steinbrink K, Enk AH. Dendritic cells as a tool to induce anergic and regulatory T cells.  Trends Immunol. 2001;  22 394-400
    CrossrefPubMedGoogle Scholar
  • 28 Cella M, Jarrossay D, Facchetti F, Alebardi O, Nakajima H, Lanzavecchia A, Colonna M. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon.  Nat Med. 1999;  5 919-923
    CrossrefPubMedGoogle Scholar
  • 29 Siegal FP, Kadowaki N, Shodell M, Fitzgerald-Bocarsly FA, Shah K, Ho S, Antonenko S, Liu YJ. The nature of the principal type 1 interferon-producing cells in human blood.  Science. 1999;  284 1835-1837
    CrossrefPubMedGoogle Scholar
  • 30 Chang CC, Wright A, Punnonen J. Monocyte-derived CD1a+ and CD1a- dendritic cell subsets differ in their cytokine production profiles, susceptibilities to transfection, and capacities to direct Th cell differentiation.  J Immunol. 2000;  165 3584-3591
    PubMedGoogle Scholar
  • 31 Ito T, Amakawa R, Inaba M, Ikehara S, Inaba K, Fukuhara S. Differential regulation of human blood dendritic cell subsets by IFNs.  J Immunol. 2001;  166 2961-2969
    PubMedGoogle Scholar
  • 32 Woodhead MA, Macfarlane JT, MacCracken JS, Rose DH, Finch RG. Prospective study of the aetiology and outcome of pneumonia in the community.  Lancet. 1987;  211 ((8534)) 671-674
    PubMedGoogle Scholar
  • 33 Marrie TJ. Bacteraemic pneumococcal pneumonia: a continuously evolving disease.  J Infect. 1992;  24 247-255
    CrossrefPubMedGoogle Scholar
  • 34 Bouter KP, Diepersloot RJ, Romunde LK van, Uitslager R, Masurel N, Hoekstra JB, Erkelens DW. Effect of epidemic influenza on ketoacidosis, pneumonia and death in diabetes mellitus: a hospital register survey of 1976-1979 in The Netherlands.  Diabetes Res Clin Pract. 1991;  12 61-68
    CrossrefPubMedGoogle Scholar
  • 35 Kass EH. Bacteriuria and the diagnosis of infections of the urinary tract; with observations on the use of methionine as a urinary antiseptic.  AMA Arch Intern Med. 1957;  100 709-714
    PubMedGoogle Scholar
  • 36 Hansen RO. Bacteriuria in diabetic and non-diabetic out-patients.  Acta Med Scand. 1964;  176 721-730
    PubMedGoogle Scholar
  • 37 Alexiewicz JM, Kumar D, Smogorzewski M, Klin M, Massry SG. Polymorphonuclear leukocytes in non-insulin-dependent diabetes mellitus: abnormalities in metabolism and function.  Ann Intern Med. 1999;  123 919-924
    PubMedGoogle Scholar
  • 38 Bouter KP, Meyling FH, Hoekstra JB, Masurel N, Erkelens DW, Diepersloot RJ. Influence of blood glucose levels on peripheral lymphocytes in patients with diabetes mellitus.  Diabetes Res. 1992;  19 77-80
    PubMedGoogle Scholar
  • 39 Valerius NH, Eff C, Hansen NE, Karle H, Nerup J, Soeberg B, Sorensen SF. Neutrophil and lymphocyte function in patients with diabetes mellitus.  Acta Med Scand. 1982;  211 463-467
    PubMedGoogle Scholar
  • 40 Teig N, Moses D, Gieseler S, Schauer U. Age-related changes in human blood dendritic cell subpopulations.  Scand J Immunol. 2002;  55 453-457
    CrossrefPubMedGoogle Scholar
  • 41 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;  122 220-128
    CrossrefPubMedGoogle Scholar
  • 42 Narbutt J, Lesiak A, Zak-Prelich M, Wozniacka A, Sysa-Jedrzejowska A, Tybura M, Robak T, Smolewski P. The distribution of peripheral blood dendritic cells assayed by a new panel of anti-BDCA monoclonal antibodies in healthy representatives of the polish population.  Cell Mol Biol Lett. 2004;  9 497-509
    PubMedGoogle Scholar
  • 43 Cederblad B, Blomberg S, Vallin H, Perers A, Alm GV, Ronnblom L. Patients with systemic lupus erythematosus have reduced numbers of circulating natural interferon-alpha- producing cells.  J Autoimm. 1998;  11 465-470
    PubMedGoogle Scholar
  • 44 Jongbloed SL, Lebre MC, Fraser AR, Gracie JA, Sturrock RD, Tak PP, McInnes IB. Enumeration and phenotypical analysis of distinct dendritic cell subsets in psoriatic arthritis and rheumatoid arthritis.  Arth Res. 2005;  , Ther 8 R15
    PubMedGoogle Scholar
  • 45 Kunitani H, Shimizu Y, Murata H, Higuchi K, Watanabe A. Phenotypic analysis of circulating and intrahepatic dendritic cell subsets in patients with chronic liver diseases.  Journal of Hepatology. 2002;  36 734-741
    CrossrefPubMedGoogle Scholar
  • 46 Yilmaz A, Weber J, Cicha I, Stumpf C, Klein M, Raithel D, Daniel WG, Garlichs CD. Decrease in circulating myeloid dendritic cell precursors in coronary artery disease.  J Am Coll Cardiol. 2006;  48 70-80
    CrossrefPubMedGoogle Scholar
  • 47 Blondet JJ, Beilman GJ. Glycemic control and prevention of perioperative infection.  Curr Opin Crit Care. 2007;  13 421-427
    CrossrefPubMedGoogle Scholar
  • 48 Tennenberg SD, Finkenauer R, Dwivedi A. Absence of lipopolysaccharide-induced inhibition of neutrophil apoptosis in patients with diabetes.  Arch Surg. 1999;  134 1229-1233
    PubMedGoogle Scholar
  • 49 Catalan MP, Reyero A, Egido J, Ortiz A. Acceleration of neutrophil apoptosis by glucose-containing peritoneal dialysis solutions: role of caspases.  J Am Soc Nephrol. 2001;  12 2442-2449
    PubMedGoogle Scholar
  • 50 Donaghy H, Pozniak A, Gazzard B, Qazi N, Gilmour J, Gotch F, Patterson S. Loss of blood CD11c(+) myeloid and CD11c(-) plasmacytoid dendritic cells in patients with HIV-1 infection correlates with HIV-1 RNA virus load.  Blood. 2001;  15 2574-2576
    PubMedGoogle Scholar
  • 51 Chehimi J, Campbell DE, Azzoni L, Bacheller D, Papasavvas E, Jerandi G, Mounzer K, Kostman J, Trinchieri G, Montaner LJ. Persistent decreases in blood plasmacytoid dendritic cell number and function despite effective highly active antiretroviral therapy and increased blood myeloid dendritic cells in HIV-infected individuals.  J Immun. 2002;  168 4796-4801
    PubMedGoogle Scholar
  • 52 Summers KL, Marleau AM, Mahon JL, MacManus R, Hramiak I, Singh B. Reduced IFN-alpha secretion by blood dendritic cells in human diabetes.  Clin Immun. 2006;  121 81-89
    PubMedGoogle Scholar
  • 53 Dunaif A. Insulin resistance in women with polycystic ovary syndrome.  Fertil Steril. 2006;  86 (Suppl 1) S13-14
    PubMedGoogle Scholar

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PD Dr. med. C.C. Seifarth

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