Dysregulated immunologic landscape of early host response in melioidosis.
Rongkard P., Xia L., Kronsteiner B., Yimthin T., Phunpang R., Dulsuk A., Hantrakun V., Wongsuvan G., Chamnan P., Lovelace-Macon L., Marchi E., Day NP., Shojaie A., Limmathurotsakul D., Chantratita N., Klenerman P., Dunachie SJ., West TE., Gharib SA.
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 melioidosis patients and 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 signaling responses compared to other infections. Mortality in melioidosis was associated with excessive inflammation, up-regulated type 2 immune responses and a dramatic decrease in T cell-mediated immunity compared to survivors. We identified and independently confirmed a five-gene predictive set classifying fatal melioidosis (validation cohort: an area under the receiver operating characteristic curve 0.83, 95% CI: 0.67-0.99). In conclusion, 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.