ACTIVATION OF CYTOTOXIC LYMPHOCYTES IN PATIENTS WITH SCRUB TYPHUS

MAAIKE DE FOST Laboratory of Experimental Internal Medicine and Department of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Medicine, Udon Thani General Hospital, Udon Thani, Thailand; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom

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WIRONGRONG CHIERAKUL Laboratory of Experimental Internal Medicine and Department of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Medicine, Udon Thani General Hospital, Udon Thani, Thailand; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom

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KRIANGSAK PIMDA Laboratory of Experimental Internal Medicine and Department of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Medicine, Udon Thani General Hospital, Udon Thani, Thailand; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom

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ARJEN M. DONDORP Laboratory of Experimental Internal Medicine and Department of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Medicine, Udon Thani General Hospital, Udon Thani, Thailand; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom

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NICHOLAS J. WHITE Laboratory of Experimental Internal Medicine and Department of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Medicine, Udon Thani General Hospital, Udon Thani, Thailand; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom

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TOM VAN DER POLL Laboratory of Experimental Internal Medicine and Department of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Medicine, Udon Thani General Hospital, Udon Thani, Thailand; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom

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Thai patients with scrub typhus caused by the intracellular pathogen Orientia tsutsugamushi displayed elevated plasma concentrations of granzymes A and B, interferon-γ (IFN)-γ–inducible protein 10, and monokine induced by IFN-γ. These data suggest that activation of cytotoxic lymphocytes is part of the early host response to scrub typhus.

Author Notes

  • 1

    Seong SY, Choi MS, Kim IS, 2001. Orientia tsutsugamushi infection: overview and immune responses. Microbes Infect 3 :11–21.

  • 2

    Silpapojakul K, Chupuppakarn S, Yuthasompob S, Varachit B, Chaipak D, Borkerd T, 1991. Scrub and murine typhus in children with obscure fever in the tropics. Pediatr Infect Dis J 10 :200–203.

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    Raupach B, Kaufmann SH, 2001. Immune responses to intracellular bacteria. Curr Opin Immunol 13 :417–428.

  • 4

    Chierakul W, de Fost M, Suputtamongkol Y, Limpaiboon R, Dondorp A, White NJ, van der Poll T, 2004. Differential expression of interferon (IFN)-γ and IFN-γ-inducing cytokines in Thai patients with scrub typhus or leptospirosis. Clin Immunol 113 :140–144.

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    Russell JH, Ley TJ, 2002. Lymphocyte-mediated cytotoxicity. Annu Rev Immunol 20 :323–370.

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    Farber JM, 1997. Mig and IP-10: CXC chemokines that target lymphocytes. J Leukoc Biol 61 :246–257.

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    Brown GW, Shirai A, Rogers C, Groves MG, 1983. Diagnostic criteria for scrub typhus: probability values for immunofluorescent antibody and Proteus OXK agglutinin titers. Am J Trop Med Hyg 32 :1101–1107.

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  • 8

    Loetscher M, Gerber B, Loetscher P, Jones SA, Piali L, Clark-Lewis I, Baggiolini M, Moser B, 1996. Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes. J Exp Med 184 :963–969.

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  • 9

    Spaeny-Dekking EH, Hanna WL, Wolbink AM, Wever PC, Kummer AJ, Swaak AJ, Middeldorp JM, Huisman HG, Froelich CJ, Hack CE, 1998. Extracellular granzymes A and B in humans: detection of native species during CTL responses in vitro and in vivo.J Immunol 160 :3610–3616.

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  • 10

    Wever PC, Spaeny LH, van der Vliet HJ, Rentenaar RJ, Wolbink AM, Surachno J, Wertheim PM, Schellekens PT, Hack CE, ten Berge IJ, 1999. Expression of granzyme B during primary cytomegalovirus infection after renal transplantation. J Infect Dis 179 :693–696.

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  • 11

    Lauw FN, Simpson AJ, Hack CE, Prins JM, Wolbink AM, van Deventer SJ, Chaowagul W, White NJ, van der Poll T, 2000. Soluble granzymes are released during human endotoxemia and in patients with severe infection due to gram-negative bacteria. J Infect Dis 182 :206–213.

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  • 12

    Lauw FN, Simpson AJ, Prins JM, Smith MD, Kurimoto M, van Deventer SJ, Speelman P, Chaowagul W, White NJ, van der Poll T, 1999. Elevated plasma concentrations of interferon (IFN)-gamma and the IFN-gamma-inducing cytokines interleukin (IL)-18, IL-12, and IL-15 in severe melioidosis. J Infect Dis 180 :1878–1885.

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