Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Lipoteichoic Acid Suppresses Effector T Cells Induced by Staphylococcus aureus-Pulsed Dendritic Cells

  • Son, Young Min (Animal Science and Biotechnology Major, Department of Agricultural Biotechnology, and Research Institute for Agriculture and Life Sciences, Seoul National University) ;
  • Song, Ki-Duk (Center for Food and Bioconvergence, Seoul National University) ;
  • Park, Sung-Moo (Animal Science and Biotechnology Major, Department of Agricultural Biotechnology, and Research Institute for Agriculture and Life Sciences, Seoul National University) ;
  • Han, Seung Hyun (Department of Oral Microbiology and Immunology, and Dental Research Institute, School of Dentistry, Seoul National University) ;
  • Yun, Cheol-Heui (Animal Science and Biotechnology Major, Department of Agricultural Biotechnology, and Research Institute for Agriculture and Life Sciences, Seoul National University)
  • Received : 2013.02.06
  • Accepted : 2013.03.27
  • Published : 2013.07.28
Download PDF
⟨ Previous Next ⟩

Abstract

Lipoteichoic acid (LTA), uniquely expressed on gram-positive bacteria, is recognized by Toll-like receptor 2 (TLR2) on not only antigen-presenting cells but also activated T cells. Therefore, it is reasonable to assume that LTA is acting on T cells. However, little is known about the effect of LTA on T-cell regulation. In the present study, we investigated the immunomodulatory effects of LTA on $CD4^+$ T cells. Effector $CD4^+$ T cells, induced after co-culture with S. aureus-pulsed dendritic cells, produced high levels of interferon-${\gamma}$, CD25, CD69, and TLRs 2 and 4. When effector $CD4^+$ T cells were treated with LTA, the expressions of the membrane-bound form of transforming growth factor (TGF)-${\beta}$ and forkhead box P3 increased. Coincidently, the proliferation of effector $CD4^+$ T cells was declined after LTA treatment. When TGF-${\beta}$ signaling was blocked by the TGF-${\beta}$ receptor 1 kinase inhibitor, LTA failed to suppress the proliferation of effector $CD4^+$ T cells. Therefore, the present results suggest that LTA suppresses the activity of effector $CD4^+$ T cells by enhancing TGF-${\beta}$ production.

Keywords

References

  1. Aderem A, Ulevitch RJ. 2000. Toll-like receptors in the induction of the innate immune response. Nature 406: 782-787. https://doi.org/10.1038/35021228
  2. Akira S, Takeda K. 2004. Toll-like receptor signalling. Nat. Rev. Immunol. 4: 499-511. https://doi.org/10.1038/nri1391
  3. Akira S, Uematsu S, Takeuchi O. 2006. Pathogen recognition and innate immunity. Cell 124: 783-801. https://doi.org/10.1016/j.cell.2006.02.015
  4. Biswas SK, Lopez-Collazo E. 2009. Endotoxin tolerance: new mechanisms, molecules and clinical significance. Trends Immunol. 30: 475-487. https://doi.org/10.1016/j.it.2009.07.009
  5. Caramalho I, Lopes-Carvalho T, Ostler D, Zelenay S, Haury M, Demengeot J. 2003. Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide. J. Exp. Med. 197: 403-411. https://doi.org/10.1084/jem.20021633
  6. Chen Q, Davidson TS, Huter EN, Shevach EM. 2009. Engagement of TLR2 does not reverse the suppressor function of mouse regulatory T cells, but promotes their survival. J. Immunol. 183: 4458-4466. https://doi.org/10.4049/jimmunol.0901465
  7. Crellin NK, Garcia RV, Hadisfar O, Allan SE, Steiner TS, Levings MK. 2005. Human CD4+ T cells express TLR5 and its ligand flagellin enhances the suppressive capacity and expression of FOXP3 in CD4+CD25+ T regulatory cells. J. Immunol. 175: 8051-8059.
  8. Dieter K. 2007. Expression and function of toll-like receptors in T lymphocytes. Curr. Opin. Immunol. 19: 39-45. https://doi.org/10.1016/j.coi.2006.11.007
  9. Dolganiuc A, Garcia C, Kodys K, Szabo G. 2006. Distinct toll-like receptor expression in monocytes and T cells in chronic HCV infection. World J. Gastroenterol 12: 1198-1204.
  10. Dziarski R, Gupta D. 2000. Role of MD-2 in TLR2- and TLR4-mediated recognition of gram-negative and gram-positive bacteria and activation of chemokine genes. J. Endotoxin Res. 6: 401-405. https://doi.org/10.1177/09680519000060050101
  11. Foster TJ. 2005. Immune evasion by staphylococci. Nat. Rev. Microbiol. 3: 948-958. https://doi.org/10.1038/nrmicro1289
  12. Gelman AE, Zhang J, Choi Y, Turka LA. 2004. Toll-like receptor ligands directly promote activated CD4+ T cell survival. J. Immunol. 172: 6065-6073.
  13. Han SH, Kim JH, Martin M, Michalek SM, Nahm MH. 2003. Pneumococcal lipoteichoic acid (LTA) is not as potent as staphylococcal LTA in stimulating toll-like receptor 2. Infect. Immun. 71: 5541-5548. https://doi.org/10.1128/IAI.71.10.5541-5548.2003
  14. Hosono M, de Boer OJ, van der Wal AC, van der Loos CM, Teeling P, Piek JJ, et al. 2003. Increased expression of T cell activation markers (CD25, CD26, CD40L, and CD69) in atherectomy specimens of patients with unstable angina and acute myocardial infarction. Atherosclerosis 168: 73-80. https://doi.org/10.1016/S0021-9150(03)00024-8
  15. Huff E. 1982. Lipoteichoic acid, a major a mphiphile of gram-positive bacteria that is not readily extractable. J. Bacteriol. 149: 399-402.
  16. Imanishi T, Hara H, Suzuki S, Suzuki N, Akira S, Saito T. 2007. Cutting edge: TLR2 directly triggers Th1 effector functions. J. Immunol. 178: 6715-6719.
  17. Jacinto R, Hartung T, McCall C, Li L. 2002. Lipopolysaccharideand lipoteichoic acid-induced tolerance and cross-tolerance: distinct alterations in IL-1 receptor-associated kinase. J. Immunol. 168: 6136-6141.
  18. Kaisho T, Akira S. 2003. Regulation of dendritic cell function through toll-like receptors. Curr. Molec. Med. 3: 759-771. https://doi.org/10.2174/1566524033479366
  19. Komai-Koma M, Jones L, Ogg GS, Xu D, Liew FY. 2004. TLR2 is expressed on activated T cells as a costimulatory receptor. Proc. Natl. Acad. Sci. USA 101: 3029-3034. https://doi.org/10.1073/pnas.0400171101
  20. Lawrence PK, Rokbi B, Arnaud-Barbe N, Sutten EL, Norimine J, Lahmers KK, et al. 2012. CD4 T cell antigens from Staphylococcus aureus Newman strain identified following immunization with heat-killed bacteria. Clin. Vaccine Immunol. 19: 477-489. https://doi.org/10.1128/CVI.05642-11
  21. Leiba M, Cahalon L, Shimoni A, Lider O, Zanin-Zhorov A, Hecht I, et al. 2006. Halofuginone inhibits $NF-{\kappa}B$ and p38 MAPK in activated T cells. J. Leukocyte Biol. 80: 399-406. https://doi.org/10.1189/jlb.0705409
  22. Liu H, Komai-Koma M, Xu D, Liew FY. 2006. Toll-like receptor 2 signaling modulates the functions of CD4+CD25+ regulatory T cells. Proc. Natl. Acad. Sci. USA 103: 7048-7053. https://doi.org/10.1073/pnas.0601554103
  23. Lombardi V, Van Overtvelt L, Horiot S, Moingeon P. 2009. Human dendritic cells stimulated via TLR7 and/or TLR8 induce the sequential production of Il-10, IFN-gamma, and IL-17A by naive CD4+ T cells. J. Immunol. 182: 3372-3379. https://doi.org/10.4049/jimmunol.0801969
  24. Mandron M, Aries M-F, Brehm RD, Tranter HS, Acharya KR, Charveron M, et al. 2006. Human dendritic cells conditioned with Staphylococcus aureus enterotoxin B promote TH2 cell polarization. J. Allergy Clin. Immunol. 117: 1141-1147.
  25. Morath S, von Aulock S, Hartung T. 2005. Structure/function relationships of lipoteichoic acids. J. Endotoxin Res. 11: 348-356. https://doi.org/10.1177/09680519050110061001
  26. Nakamura K, Kitani A, Strober W. 2001. Cell contactdependent immunosuppression by Cd4+Cd25+regulatory T cells is mediated by cell surface-bound transforming growth factor ${\beta}$. J. Exp. Med. 194: 629-644. https://doi.org/10.1084/jem.194.5.629
  27. Netea MG, Sutmuller R, Hermann C, Van der Graaf CAA, Van der Meer JWM, Van Krieken JH, et al. 2004. Toll-like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cells. J. Immunol. 172: 3712-3718.
  28. Poltorak A, He X, Smirnova I, Liu M-Y, Huffel CV, Du X, et al. 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282: 2085-2088. https://doi.org/10.1126/science.282.5396.2085
  29. Re F, Strominger JL. 2001. Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells. J. Biol. Chem. 276: 37692-37699. https://doi.org/10.1074/jbc.M105927200
  30. Sakaguchi S, Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T. 2009. Regulatory T cells: how do they suppress immune responses? Int. Immunol. 21: 1105-1111. https://doi.org/10.1093/intimm/dxp095
  31. Son YM, Ahn SM, Jang MS, Moon YS, Kim SH, Cho K-K, et al. 2008. Immunomodulatory effect of resistin in human dendritic cells stimulated with lipoteichoic acid from Staphylococcus aureus. Biochem. Biophys. Res. Commun. 376: 599-604. https://doi.org/10.1016/j.bbrc.2008.09.037
  32. Sutmuller RP, den Brok MH, Kramer M, Bennink EJ, Toonen LW, Kullberg BJ, et al. 2006. Toll-like receptor 2 controls expansion and function of regulatory T cells. J. Clin. Invest. 116: 485-494. https://doi.org/10.1172/JCI25439
  33. van Beelen AJ, Zelinkova Z, Taanman-Kueter EW, Muller FJ, Hommes DW, Zaat SAJ, et al. 2007. Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells. Immunity 27: 660-669. https://doi.org/10.1016/j.immuni.2007.08.013
  34. Wan Y, Flavell R. 2008. $TGF-{\beta}$ and regulatory T cell in immunity and autoimmunity. J. Clin. Immunol. 28: 647-659. https://doi.org/10.1007/s10875-008-9251-y
  35. Ye Z-J, Zhou Q, Zhang J-C, Li X, Wu C, Qin S-M, et al. 2011. CD39+ Regulatory T cells suppress generation and differentiation of Th17 cells in human malignant pleural effusion via a LAP-dependent mechanism. Respir. Res. 12: 77. https://doi.org/10.1186/1465-9921-12-77
  36. Yoshimura A, Lien E, Ingalls RR, Tuomanen E, Dziarski R, Golenbock D. 1999. Cutting edge: recognition of gram-positive bacterial cell wall components by the innate immune system occurs via toll-like receptor 2. J. Immunol. 163: 1-5.
  37. Zanin-Zhorov A, Cahalon L, Tal G, Margalit R, Lider O, Cohen IR. 2006. Heat shock protein 60 enhances CD4+ CD25+ regulatory T cell function via innate TLR2 signaling. J. Clin. Invest. 116: 2022-2032. https://doi.org/10.1172/JCI28423

Cited by

  1. Oral Administration of Flavonifractor plautii, a Bacteria Increased With Green Tea Consumption, Promotes Recovery From Acute Colitis in Mice via Suppression of IL-17 vol.7, pp.None, 2013, https://doi.org/10.3389/fnut.2020.610946