Volume 71, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Rickettsiae cause systemic infections such as Rocky Mountain spotted fever and boutonneuse fever. The main cellular target of these obligately intracellular bacteria is the endothelium. T lymphocytes are the most important effectors of immunity, and the CXCR3 ligands CXCL9 and CXCL10 may play an important role in the T cell-mediated clearance of rickettsiae from the infected vasculature as suggested by recent expression studies. Here we showed that antibody-mediated neutralization of CXCL9 and CXCL10, and CXCR3 gene knockout, had no effect on survival or bacterial loads of mice infected with rickettsiae. We also demonstrated that rickettsiae triggered the endothelial expression of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 . These findings suggested that antigenic presentation by endothelial cells together with an endothelial inflammatory phenotype induced by the rickettsial infection may be sufficient to arrest T cells and trigger their anti-rickettsial effector mechanisms without the need for chemokines.


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  1. Heinzen RA, Grieshaber SS, Van Kirk LS, Devin CJ, 1999. Dynamics of actin-based movement by Rickettsia rickettsii in Vero cells. Infect Immun 67 : 4201–4207.
  2. Heinzen RA, Hayes SF, Peacock MG, Hackstadt T. 1993. Directional actin polymerization associated with spotted fever group rickettsia infection of Vero cells. Infect Immun 61 : 1926–1935.
  3. Van Kirk LS, Hayes SF, Heinzen RA, 2000. Ultrastructure of Rickettsia rickettsii actin tails and localization of cytoskeletal proteins. Infect Immun 68 : 4706–4713.
  4. Teysseire N, Chiche-Portiche C, Raoult D, 1992. Intracellular movements of Rickettsia conorii and R. typhi based on actin polymerization. Res Microbiol 143 : 821–829.
  5. Walker DH, 1995. Rocky Mountain spotted fever: a seasonal alert. Clin Infect Dis 20 : 1111–1117.
  6. Walker DH, Lane TW. 1988. Rocky Mountain spotted fever: clinical signs, symptoms, and pathophysiology. Walker DH, ed. Biology of Rickettsial Diseases. Boca Raton, FL: CRC Press, 63–78.
  7. Feng H, Popov VL, Yuoh G, Walker DH, 1997. Role of T lymphocyte subsets in immunity to spotted fever group rickettsiae. J Immunol 58 : 5314–5320.
  8. Walker DH, Olano JP, Feng HM, 2001. Critical role of cytotoxic T lymphocytes in immune clearance of rickettsial infection. Infect Immun 69 : 1841–1846.
  9. Herrero-Herrero JI, Walker DH, Ruiz-Beltran R, 1987. Immunohistochemical evaluation of the cellular immune response to Rickettsia conorii in taches noires. J Infect Dis 155 : 802–805.
  10. Valbuena G, Bradford W, Walker DH, 2003. Expression analysis of the T-cell-targeting chemokines CXCL9 and CXCL10 in mice and humans with endothelial infections caused by rickettsiae of the spotted fever group. Am J Pathol 163 : 1357–1369.
  11. Walker DH, Cain BG, 1980. The rickettsial plaque. Evidence for direct cytopathic effect of Rickettsia rickettsii. Lab Invest 43 : 388–396.
  12. Reed KJ, Muench H, 1938. A simple method of estimating fifty percent endpoints. Am J Hyg 27 : 493–497.
  13. Walker DH, Popov VL, Wen J, Feng HM, 1994. Rickettsia conorii infection of C3H/HeN mice. A model of endothelial-target rickettsiosis. Lab Invest 70 : 358–368.
  14. Feng HM, Wen J, Walker DH, 1993. Rickettsia australis infection: a murine model of a highly invasive vasculopathic rickettsiosis. Am J Pathol 142 : 1471–1482.
  15. Liu MT, Armstrong D, Hamilton TA, Lane TE, 2001. Expression of Mig (monokine induced by interferon-gamma) is important in T lymphocyte recruitment and host defense following viral infection of the central nervous system. J Immunol 166 : 1790–1795.
  16. Liu MT, Chen BP, Oertel P, Buchmeier MJ, Armstrong D, Hamilton TA, Lane TE, 2000. The T cell chemoattractant IFN-inducible protein 10 is essential in host defense against viral-induced neurologic disease. J Immunol 165 : 2327–2330.
  17. Tannenbaum CS, Tubbs R, Armstrong D, Finke JH, Bukowski RM, Hamilton TA, 1998.The CXC chemokines IP-10 and Mig are necessary for IL-12-mediated regression of the mouse RENCA tumor. J Immunol 161 : 927–932.
  18. O’Connell KA, Edidin M, 1990. A mouse lymphoid endothelial cell line immortalized by simian virus 40 binds lymphocytes and retains functional characteristics of normal endothelial cells. J Immunol 144 : 521–525.
  19. Farber JM, 1997. Mig and IP-10: CXC chemokines that target lymphocytes. J Leukoc Biol 61 : 246–257.
  20. Piali L, Weber C, LaRosa G, Mackay CR, Springer TA, Clark-Lewis I, Moser B, 1998. The chemokine receptor CXCR3 mediates rapid and shear-resistant adhesion-induction of effector T lymphocytes by the chemokines IP10 and Mig. Eur J Immunol 28 : 961–972.
  21. Miura M, Morita K, Kobayashi H, Hamilton TA, Burdick MD, Streiter RM, Fairchild RL, 2001. Monokine induced by IFN-gamma is a dominant factor directing T cells into murine cardiac allografts during acute rejection. J Immunol 167 : 3494–3504.
  22. Hancock WW, Gao W, Csizmadia V, Faia KL, Shemmeri N, Luster AD, 2001. Donor-derived IP-10 initiates development of acute allograft rejection. J Exp Med 193 : 975–980.
  23. Hancock WW, Lu B, Gao W, Csizmadia V, Faia K, King JA, Smiley ST, Ling M, Gerard NP, Gerard C, 2000. Requirement of the chemokine receptor CXCR3 for acute allograft rejection. J Exp Med 192 : 1515–1520.
  24. Khan IA, MacLean JA, Lee FS, Casciotti L, DeHaan E, Schwartzman JD, Luster AD, 2000. IP-10 is critical for effector T cell trafficking and host survival in Toxoplasma gondii infection. Immunity 12 : 483–494.
  25. Alon R, Feigelson S, 2002. From rolling to arrest on blood vessels: leukocyte tap dancing on endothelial integrin ligands and chemokines at sub-second contacts. Semin Immunol 14: 93–104.
  26. Johnston B, Butcher EC, 2002. Chemokines in rapid leukocyte adhesion triggering and migration. Semin Immunol 14 : 83–92.
  27. Kaplanski G, Teysseire N, Farnarier C, Kaplanski S, Lissitzky JC, Durand JM, Soubeyrand J, Dinarello CA, Bongrand P, 1995. IL-6 and IL-8 production from cultured human endothelial cells stimulated by infection with Rickettsia conorii via a cell-associated IL-1 alpha-dependent pathway. J Clin Invest 96 : 2839–2844.
  28. Sporn LA, Marder VJ, 1996. Interleukin-1 alpha production during Rickettsia rickettsii infection of cultured endothelial cells: potential role in autocrine cell stimulation. Infect Immun 64 : 1609–1613.
  29. Dignat-George F, Teysseire N, Mutin M, Bardin N, Lesaule G, Raoult D, Sampol J, 1997. Rickettsia conorii infection enhances vascular cell adhesion molecule-1- and intercellular adhesion molecule-1-dependent mononuclear cell adherence to endothelial cells. J Infect Dis 175 : 1142–1152.
  30. Sporn LA, Lawrence SO, Silverman DJ, Marder VJ, 1993. E-selectin-dependent neutrophil adhesion to Rickettsia rickettsii-infected endothelial cells. Blood 81 : 2406–2412.
  31. Constantin G, Majeed M, Giagulli C, Piccio L, Kim JY, Butcher EC, Laudanna C, 2000. Chemokines trigger immediate beta2 integrin affinity and mobility changes: differential regulation and roles in lymphocyte arrest under flow. Immunity 13 : 759–769.
  32. Dustin ML, Springer TA, 1989. T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature 341 : 619–624.
  33. van Kooyk Y, van de Wielvan Kemenade, Weder P, Kuijpers TW, Figdor CG, 1989. Enhancement of LFA-1-mediated cell adhesion by triggering through CD2 or CD3 on T lymphocytes. Nature 342 : 811–813.
  34. Chan BM, Wong JG, Rao A, Hemler ME, 1991. T cell receptor-dependent, antigen-specific stimulation of a murine T cell clone induces a transient, VLA protein-mediated binding to extracellular matrix. J Immunol 147 : 398–404.
  35. Wysocki J, Issekutz TB, 1992. Effect of T cell activation on lymphocyte-endothelial cell adherence and the role of VLA-4 in the rat. Cell Immunol 140 : 420–431.
  36. Savinov AY, Wong FS, Stonebraker AC, Chervonsky AV, 2003. Presentation of antigen by endothelial cells and chemoattraction are required for homing of insulin-specific CD8+ T cells. J Exp Med 197 : 643–656.
  37. Christopherson KW, Hood AF, Travers JB, Ramsey H, Hromas RA, 2003. Endothelial induction of the T-cell chemokine CCL21 in T-cell autoimmune diseases. Blood 101 : 801–806.
  38. Weninger W, Carlsen HS, Goodarzi M, Moazed F, Crowley MA, Baekkevold ES, Cavanagh LL, von Andrian UH, 2003. Naive T cell recruitment to nonlymphoid tissues: a role for endothelium-expressed CC chemokine ligand 21 in autoimmune disease and lymphoid neogenesis. J Immunol 170 : 4638–4648.
  39. Alt C, Laschinger M, Engelhardt B, 2002. Functional expression of the lymphoid chemokines CCL19 (ELC) and CCL 21 (SLC) at the blood-brain barrier suggests their involvement in G-protein-dependent lymphocyte recruitment into the central nervous system during experimental autoimmune encephalomyelitis. Eur J Immunol 32 : 2133–2144.

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  • Received : 16 Dec 2003
  • Accepted : 28 Jan 2004

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