Skip to main content

Advertisement

Log in

Modulation of dendritic cells and toll-like receptors by marathon running

  • Original Article
  • Published:
European Journal of Applied Physiology Aims and scope Submit manuscript

Abstract

The focus of this study was to assess exercise-induced alterations of circulating dendritic cell (DC) subpopulations and toll-like receptor (TLR) expression after marathon running. Blood sampling was performed in 15 obese non-elite (ONE), 16 lean non-elite (LNE) and 16 lean elite (LE) marathon runners pre- and post-marathon as well as 24 h after the race. Circulating DC-fractions were measured by flow-cytometry analyzing myeloid DCs (BDCA-1+) and plasmacytoid DCs (BDCA-2+). We further analyzed the (TLR) -2/-4/-7 in peripheral blood mononuclear cells (rt-PCR/Western Blot) and the cytokines CRP, IL-6, IL-10, TNF-α and oxLDL by ELISA. After the marathon, BDCA-1 increased significantly in all groups [LE (pre/post): 0.35/0.47%; LNE: 0.26/0.50% and ONE: 0.30/0.49%; all p < 0.05]. In contrast, we found a significant decrease for BDCA-2 directly after the marathon (LE: 0.09/0.01%; LNE: 0.12/0.03% and ONE: 0.10/0.02%; all p < 0.05). Levels of TLR-7 mRNA decreased in all groups post-marathon (LE 44%, LNE 67% and ONE 52%; all p < 0.01), with a consecutive protein reduction (LE 31%, LNE 52%, ONE 42%; all p < 0.05) 24 h later. IL-6 and IL-10 levels increased immediately after the run, whereas increases of TNF-α and CRP-levels were seen after 24 h. oxLDL levels remained unchanged post-marathon. In our study population, we did not find any relevant differences regarding training level or body weight. Prolonged endurance exercise induces both pro- and anti-inflammatory cytokines. Anti-inflammatory cytokines, such as IL-10, may help to prevent excessive oxidative stress. Marathon running is associated with alterations of DC subsets and TLR-expression independent of training level or body weight. Myeloid and plasmacytoid DCs are differently affected by the excessive physical stress. Immunomodulatory mechanisms seem to play a key role in the response and adaptation to acute excessive exercise.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B (2006) Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 17:4–12

    PubMed  CAS  Google Scholar 

  • Binder CJ, Hartvigsen K, Chang MK, Miller M, Broide D, Palinski W, Curtiss LK, Corr M, Witztum JL (2004) IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis. J Clin Invest 114:427–437

    PubMed  CAS  Google Scholar 

  • Carpenter S, O’Neill LA (2007) How important are Toll-like receptors for antimicrobial responses? Cell Microbiol 9:1891–1901

    Article  PubMed  CAS  Google Scholar 

  • Di Domizio J, Blum A, Gallagher-Gambarelli M, Molens JP, Chaperot L, Plumas J (2009) TLR7 stimulation in human plasmacytoid dendritic cells leads to the induction of early IFN-inducible genes in the absence of type I IFN. Blood 114:1794–1802

    Article  PubMed  CAS  Google Scholar 

  • Flegg PJ (1988) Risk of upper respiratory tract infection and malaria prophylaxis. Br Med J (Clin Res Ed) 296:1329

    Article  CAS  Google Scholar 

  • Hanssen H, Nickel T, Drexel V, Hertel G, Emslander I, Sisic Z, Lorang D, Schuster T, Kotliar KE, Pressler A, Schmidt-Trucksäss A, Weis M, Halle M (2011) Exercise-induced alterations of retinal vessel diameters and cardiovascular risk reduction in obesity. Atherosclerosis 216:433–439

    Article  PubMed  CAS  Google Scholar 

  • Ilback NG, Friman G, Beisel WR, Johnson AJ, Berendt RF (1984) Modifying effects of exercise on clinical course and biochemical response of the myocardium in influenza and tularemia in mice. Infect Immun 45:498–504

    PubMed  CAS  Google Scholar 

  • Ilback NG, Crawford DJ, Neufeld HA, Friman G (1991) Does exercise stress alter susceptibility to bacterial infections? Ups J Med Sci 96:63–68

    Article  PubMed  CAS  Google Scholar 

  • Kapsenberg ML (2003) Dendritic-cell control of pathogen-driven T-cell polarization. Nat Rev Immunol 3:984–993

    Article  PubMed  CAS  Google Scholar 

  • Kasapis C, Thompson PD (2005) The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review. J Am Coll Cardiol 45:1563–1569

    Article  PubMed  CAS  Google Scholar 

  • Lancaster GI, Khan Q, Drysdale P, Wallace F, Jeukendrup AE, Drayson MT, Gleeson M (2005) The physiological regulation of toll-like receptor expression and function in humans. J Physiol 563:945–955

    Article  PubMed  CAS  Google Scholar 

  • Livak F, Petrie HT (2001) Somatic generation of antigen-receptor diversity: a reprise. Trends Immunol 22:608–612

    Article  PubMed  CAS  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408

    Article  PubMed  CAS  Google Scholar 

  • Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, Iwasaki A, Flavell RA (2004) Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci USA 101:5598–5603

    Article  PubMed  CAS  Google Scholar 

  • Malm C (2006) Susceptibility to infections in elite athletes: the S-curve. Scand J Med Sci Sports 16:4–6

    Article  PubMed  CAS  Google Scholar 

  • Narbutt J, Lesiak A, Zak-Prelich M, Wozniacka A, Sysa-Jedrzejowska A, Tybura M, Robak T, Smolewski P (2004) 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 9:497–509

    PubMed  Google Scholar 

  • Neilan TG, Januzzi JL, Lee-Lewandrowski E, Ton-Nu TT, Yoerger DM, Jassal DS, Lewandrowski KB, Siegel AJ, Marshall JE, Douglas PS, Lawlor D, Picard MH, Wood MJ (2006) Myocardial injury and ventricular dysfunction related to training levels among nonelite participants in the Boston marathon. Circulation 114:2325–2333

    Article  PubMed  Google Scholar 

  • Nickel T, Schmauss D, Hanssen H, Sicic Z, Krebs B, Jankl S, Summo C, Fraunberger P, Walli AK, Pfeiler S, Weis M (2009) oxLDL uptake by dendritic cells induces upregulation of scavenger-receptors, maturation and differentiation. Atherosclerosis 205:442–450

    Article  PubMed  CAS  Google Scholar 

  • Nickel T, Hanssen H, Sisic Z, Pfeiler S, Summo C, Schmauss D, Hoster E, Weis M (2010) Immunoregulatory effects of the flavonol quercetin in vitro and in vivo. Eur J Nutr 50:163–172

    Google Scholar 

  • Nickel T, Hanssen H, Emslander I, Drexel V, Hertel G, Schmidt-Trucksass A, Summo C, Sisic Z, Lambert M, Hoster E, Halle M, Weis M (2011) Immunomodulatory effects of aerobic training in obesity. Mediators Inflamm 2011:308965

    Article  PubMed  Google Scholar 

  • Nieman DC (1997) Risk of upper respiratory tract infection in athletes: an epidemiologic and immunologic perspective. J Athl Train 32:344–349

    PubMed  CAS  Google Scholar 

  • Nieman DC, Henson DA, Smith LL, Utter AC, Vinci DM, Davis JM, Kaminsky DE, Shute M (2001) Cytokine changes after a marathon race. J Appl Physiol 91:109–114

    PubMed  CAS  Google Scholar 

  • Oliveira M, Gleeson M (2010) The influence of prolonged cycling on monocyte Toll-like receptor 2 and 4 expression in healthy men. Eur J Appl Physiol 109:251–257

    Article  PubMed  CAS  Google Scholar 

  • Ostrowski K, Rohde T, Asp S, Schjerling P, Pedersen BK (1999) Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. J Physiol 515(Pt 1):287–291

    Article  PubMed  CAS  Google Scholar 

  • Pedersen BK, Steensberg A, Fischer C, Keller C, Ostrowski K, Schjerling P (2001a) Exercise and cytokines with particular focus on muscle-derived IL-6. Exerc Immunol Rev 7:18–31

    PubMed  CAS  Google Scholar 

  • Pedersen BK, Steensberg A, Schjerling P (2001b) Muscle-derived interleukin-6: possible biological effects. J Physiol 536:329–337

    Article  PubMed  CAS  Google Scholar 

  • Rehman J, Mills PJ, Carter SM, Chou J, Thomas J, Maisel AS (1997) Dynamic exercise leads to an increase in circulating ICAM-1: further evidence for adrenergic modulation of cell adhesion. Brain Behav Immun 11:343–351

    Article  PubMed  CAS  Google Scholar 

  • Sanchez LD, Pereira J, Berkoff DJ (2009) The evaluation of cardiac complaints in marathon runners. J Emerg Med 36:369–376

    Article  PubMed  Google Scholar 

  • Schiffer T, Montiel G, Hildebrandt U, Predel HG, Knackstedt C (2010) Der Marathonlauf als gesundheitliches Risiko? Klinikarzt 39:288–291

    Google Scholar 

  • Seibl R, Birchler T, Loeliger S, Hossle JP, Gay RE, Saurenmann T, Michel BA, Seger RA, Gay S, Lauener RP (2003) Expression and regulation of Toll-like receptor 2 in rheumatoid arthritis synovium. Am J Pathol 162:1221–1227

    Article  PubMed  CAS  Google Scholar 

  • Simpson RJ, McFarlin BK, McSporran C, Spielmann G, o Hartaigh B, Guy K (2009) Toll-like receptor expression on classic and pro-inflammatory blood monocytes after acute exercise in humans. Brain Behav Immun 23:232–239

    Article  PubMed  CAS  Google Scholar 

  • Smit JJ, Rudd BD, Lukacs NW (2006) Plasmacytoid dendritic cells inhibit pulmonary immunopathology and promote clearance of respirory syncytial virus. J Exp Med 203:1153–1159

    Article  PubMed  CAS  Google Scholar 

  • Smit JJ, Lindell DM, Boon L, Kool M, Lambrecht BN, Lukacs NW (2008) The balance between plasmacytoid DC versus conventional DC determines pulmonary immunity to virus infections. PLoS One 3:e1720

    Article  PubMed  Google Scholar 

  • Steensberg A, van Hall G, Osada T, Sacchetti M, Saltin B, Klarlund Pedersen B (2000) Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. J Physiol 529(Pt 1):237–242

    Article  PubMed  CAS  Google Scholar 

  • Suchanek O, Podrazil M, Fischerova B, Bocinska H, Budinsky V, Stejskal D, Spisek R, Bartunkova J, Kolar P (2010) Intensive physical activity increases peripheral blood dendritic cells. Cell Immunol 266:40–45

    Article  PubMed  CAS  Google Scholar 

  • Suzuki K, Nakaji S, Yamada M, Liu Q, Kurakake S, Okamura N, Kumae T, Umeda T, Sugawara K (2003) Impact of a competitive marathon race on systemic cytokine and neutrophil responses. Med Sci Sports Exerc 35:348–355

    Article  PubMed  CAS  Google Scholar 

  • Svec P, Vasarhelyi B, Paszthy B, Korner A, Kovacs L, Tulassay T, Treszl A (2007) Do regulatory T cells contribute to Th1 skewness in obesity? Exp Clin Endocrinol Diabetes 115:439–443

    Article  PubMed  CAS  Google Scholar 

  • Trivax JE, Franklin BA, Goldstein JA, Chinnaiyan KM, Gallagher MJ, de Jong AT, Colar JM, Haines DE, McCullough PA (2010) Acute cardiac effects of marathon running. J Appl Physiol 108:1148–1153

    Article  PubMed  CAS  Google Scholar 

  • Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Pais P, Varigos J, Liseng L (2004) Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 364:937–952

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported in part by the Heinrich and Lotte Muehlfenzl Foundation, which provide educational grants for young scientists.

Conflict of interest

The authors have no conflicts of interest to disclose.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thomas Nickel.

Additional information

Communicated by Susan A. Ward.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nickel, T., Emslander, I., Sisic, Z. et al. Modulation of dendritic cells and toll-like receptors by marathon running. Eur J Appl Physiol 112, 1699–1708 (2012). https://doi.org/10.1007/s00421-011-2140-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-011-2140-8

Keywords

Navigation