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Research Article

Toll-Like Receptor 2 Impairs Host Defense in Gram-Negative Sepsis Caused by Burkholderia pseudomallei (Melioidosis)

  • W. Joost Wiersinga mail,

    To whom correspondence should be addressed. E-mail: w.j.wiersinga@amc.uva.nl

    Affiliations: Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands, Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands

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  • Catharina W Wieland,

    Affiliations: Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands, Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands

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  • Mark C Dessing,

    Affiliations: Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands, Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands

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  • Narisara Chantratita,

    Affiliation: Wellcome Trust, Mahidol University, Bangkok, Thailand

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  • Allen C Cheng,

    Affiliation: Menzies School of Health Research, Darwin, Australia

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  • Direk Limmathurotsakul,

    Affiliation: Wellcome Trust, Mahidol University, Bangkok, Thailand

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  • Wirongrong Chierakul,

    Affiliation: Wellcome Trust, Mahidol University, Bangkok, Thailand

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  • Masja Leendertse,

    Affiliations: Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands, Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands

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  • Sandrine Florquin,

    Affiliation: Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands

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  • Alex F de Vos,

    Affiliations: Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands, Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands

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  • Nicholas White,

    Affiliations: Wellcome Trust, Mahidol University, Bangkok, Thailand, Center for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, England

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  • Arjen M Dondorp,

    Affiliation: Wellcome Trust, Mahidol University, Bangkok, Thailand

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  • Nicholas P Day,

    Affiliations: Wellcome Trust, Mahidol University, Bangkok, Thailand, Center for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, England

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  • Sharon J Peacock,

    Affiliations: Wellcome Trust, Mahidol University, Bangkok, Thailand, Center for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, England

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  • Tom van der Poll

    Affiliations: Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands, Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands

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  • Published: July 31, 2007
  • DOI: 10.1371/journal.pmed.0040248

About the Authors

W. Joost Wiersinga, Catharina W Wieland, Mark C Dessing, Masja Leendertse, Alex F de Vos, Tom van der Poll
Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands
W. Joost Wiersinga, Catharina W Wieland, Mark C Dessing, Masja Leendertse, Alex F de Vos, Tom van der Poll
Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands
Narisara Chantratita, Direk Limmathurotsakul, Wirongrong Chierakul, Nicholas White, Arjen M Dondorp, Nicholas P Day, Sharon J Peacock
Wellcome Trust, Mahidol University, Bangkok, Thailand
Allen C Cheng
Menzies School of Health Research, Darwin, Australia
Sandrine Florquin
Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
Nicholas White, Nicholas P Day, Sharon J Peacock
Center for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, England

Corresponding Author

Email: w.j.wiersinga@amc.uva.nl

Competing Interests

The authors have declared that no competing interests exist.

Author Contributions

WJW, CWW, NC, ACC, WC, AFdV, AMD, NPD, SJP, and TvdP designed the study. WJW, MCD, ML, and SF analysed the data. WJW, ACC, DL, and SJP enrolled patients. WJW, NC, ACC, DL, WC, AFdV, NW, AMD, NPD, SJP, and TvdP contributed to writing the paper. CWW and NC collected data or performed experiments for this study. MCD performed the MLPA technique and data analysis as mentioned in section “RNA analysis using multiplex ligation-dependent probe amplification.” DL recruited patients with sepsis caused by B. pseudomallei at Sapprasithiprasong Hospital, Ubon Radchathnai, northeastern Thailand, and collected the clinical data and blood specimens for the study. ML performed some of the ex vivo and in vitro experiments. NW helped organize the clinical study.