Dysregulated immunologic landscape of the early host response in melioidosis
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.
Authors
- Emanuele Marchi (ORCID: https://orcid.org/0000-0003-1741-9353)
- Parinya Chamnan (ORCID: https://orcid.org/0000-0002-5202-4149)
- T. Eoin West (ORCID: https://orcid.org/0000-0001-5503-7204)
- Paul Klenerman (ORCID: https://orcid.org/0000-0003-4307-9161)
- Nicholas Day (ORCID: https://orcid.org/0000-0003-2309-1171)
- Narisara Chantratita (ORCID: https://orcid.org/0000-0003-3906-7379)
- Thatcha Yimthin (ORCID: https://orcid.org/0009-0004-4489-172X)
- Lara Lovelace-Macon (ORCID: https://orcid.org/0000-0002-4884-2835)
- Rungnapa Phunpang (ORCID: https://orcid.org/0000-0001-6920-6785)
- Ali Shojaie (ORCID: https://orcid.org/0000-0001-8846-3533)
- Viriya Hantrakun (ORCID: https://orcid.org/0000-0002-6727-3404)
- Adul Dulsuk
- Barbara Kronsteiner (ORCID: https://orcid.org/0000-0003-0867-2867)
- Susanna Dunachie (ORCID: https://orcid.org/0000-0001-5665-6293)
- Sina A. Gharib (ORCID: https://orcid.org/0000-0002-2480-4367)
- Patpong Rongkard (ORCID: https://orcid.org/0000-0002-4094-5143)
- Lu Xia (ORCID: https://orcid.org/0000-0003-1561-6871)
- Gumphol Wongsuvan
- Direk Limmathurotsakul
Institutions
- University of Washington (US)
- Mahidol University (TH)
- Angkor Hospital for Children (KH)
- University of Oxford (GB)
- Medawar Building for Pathogen Research (GB)
- Sappasithiprasong Hospital (TH)
- Mahidol Oxford Tropical Medicine Research Unit (TH)
- Oxford BioMedica (United Kingdom) (GB)
- Seattle University (US)
- Michigan State University (US)
Publication Details
- Journal
- JCI Insight
- Published
- 2024-08-20
- DOI
- https://doi.org/10.1172/jci.insight.179106
- Citations
- 3
- Primary Topic
- Burkholderia infections and melioidosis
- Type
- article
- Field-Weighted Citation Impact
- 1.16
Funders
- Wellcome Trust
- National Institute for Health and Care Research
- National Institutes of Health