Dysregulated immunologic landscape of the early host response in melioidosis.

Autor:	Rongkard P; NDM Centre for Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.; Mahidol-Oxford Tropical Medicine Research Unit, Salaya, Thailand., Xia L; Department of Statistics and Probability, Michigan State University, East Lansing, USA., Kronsteiner B; NDM Centre for Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom., Yimthin T; Department of Microbiology and Immunology, Mahidol University, Bangkok, Thailand., Phunpang R; Mahidol-Oxford Tropical Medicine Research Unit, Salaya, Thailand.; Department of Microbiology and Immunology, Mahidol University, Bangkok, Thailand., Dulsuk A; Mahidol-Oxford Tropical Medicine Research Unit, Salaya, Thailand.; Department of Microbiology and Immunology, Mahidol University, Bangkok, Thailand., Hantrakun V; Mahidol-Oxford Tropical Medicine Research Unit, Salaya, Thailand., Wongsuvan G; Mahidol-Oxford Tropical Medicine Research Unit, Salaya, Thailand., Chamnan P; Sunpasitthiprasong Hospital, Ubon Ratchathani, Thailand., Lovelace-Macon L; Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, USA., Marchi E; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom., Day NP; NDM Centre for Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.; Mahidol-Oxford Tropical Medicine Research Unit, Salaya, Thailand., Shojaie A; Department of Biostatistics, University of Washington, Seattle, USA., Limmathurotsakul D; Mahidol-Oxford Tropical Medicine Research Unit, Salaya, Thailand., Chantratita N; Mahidol-Oxford Tropical Medicine Research Unit, Salaya, Thailand.; Department of Microbiology and Immunology, Mahidol University, Bangkok, Thailand., Klenerman P; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.; Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, Oxford, United Kingdom., Dunachie SJ; NDM Centre for Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.; Mahidol-Oxford Tropical Medicine Research Unit, Salaya, Thailand.; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, Oxford, United Kingdom., West TE; Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, USA.; Department of Global Health, University of Washington, Seattle, USA., Gharib SA; Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, USA.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2024 Aug 20; Vol. 9 (18). Date of Electronic Publication: 2024 Aug 20.
DOI:	10.1172/jci.insight.179106
Abstrakt:	Melioidosis, a neglected tropical infection caused by Burkholderia pseudomallei, commonly presents as pneumonia or sepsis with mortality rates up to 50% despite appropriate treatment. A better understanding of the early host immune response to melioidosis may lead to new therapeutic interventions and prognostication strategies to reduce disease burden. Whole blood transcriptomic signatures in 164 patients with melioidosis and in 70 patients with other infections hospitalized in northeastern Thailand enrolled within 24 hours following hospital admission were studied. Key findings were validated in an independent melioidosis cohort. Melioidosis was characterized by upregulation of interferon (IFN) signaling responses compared with other infections. Mortality in melioidosis was associated with excessive inflammation, enrichment of type 2 immune responses, and a dramatic decrease in T cell-mediated immunity compared with survivors. We identified and independently confirmed a 5-gene predictive set classifying fatal melioidosis (validation cohort area under the receiver operating characteristic curve 0.83; 95% CI, 0.67-0.99). This study highlights the intricate balance between innate and adaptive immunity during fatal melioidosis and can inform future precision medicine strategies for targeted therapies and prognostication in this severe infection.
Databáze:	MEDLINE
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