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.
JCI Insight. 2024 Aug 20;9(18):e179106. doi: 10.1172/jci.insight.179106.
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.
类鼻疽，一种由伯克霍尔德氏菌引起的被忽视的热带传染病，常表现为肺炎或败血症，尽管进行了适当的治疗，死亡率仍高达 50%。更好地了解宿主对类鼻疽的早期免疫反应，可能会导致新的治疗干预和预后策略，以减轻疾病负担。本研究分析了在泰国东北部住院的 164 例类鼻疽患者和 70 例其他感染患者的全血转录组特征，这些患者在入院后 24 小时内入院。关键发现已在独立的类鼻疽队列中得到验证。与其他感染相比，类鼻疽的特征是干扰素（IFN）信号反应上调。与幸存者相比，类鼻疽的死亡率与过度炎症、2 型免疫反应富集以及 T 细胞介导的免疫急剧下降有关。我们确定并独立证实了一个 5 基因预测集，可以区分致命性类鼻疽（验证队列受试者工作特征曲线下面积为 0.83；95%置信区间，0.67-0.99）。本研究强调了致命性类鼻疽期间固有免疫和适应性免疫之间的复杂平衡，并为这种严重感染的靶向治疗和预后提供了未来精准医学策略的信息。
