Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Department of Microbiology, Faculty of Public Health, Mahidol University, Bangkok, Thailand.
PLoS Negl Trop Dis. 2024 Jul 23;18(7):e0012368. doi: 10.1371/journal.pntd.0012368. eCollection 2024 Jul.
Melioidosis caused by Burkholderia pseudomallei is an infectious disease with a high mortality rate. In acute melioidosis, sepsis is a major cause of death among patients. Once the bacterium enters the bloodstream, immune system dysregulation ensues, leading to cytokine storms. In contrast to B. pseudomallei, a closely related but non-virulent strain B. thailandensis has rarely been reported to cause cytokine storms or death in patients. However, the mechanisms in which the virulent B. pseudomallei causes sepsis are not fully elucidated. It is well-documented that monocytes play an essential role in cytokine production in the bloodstream. The present study, therefore, determined whether there is a difference in the innate immune response to B. pseudomallei and B. thailandensis during infection of primary human monocytes and THP-1 monocytic cells by investigating pyroptosis, an inflammatory death pathway known to play a pivotal role in sepsis. Our results showed that although both bacterial species exhibited a similar ability to invade human monocytes, only B. pseudomallei can significantly increase the release of cytosolic enzyme lactate dehydrogenase (LDH) as well as the increases in caspase-1 and gasdermin D activations in both cell types. The results were consistent with the significant increase in IL-1β and IL-18 production, key cytokines involved in pyroptosis. Interestingly, there was no significant difference in other cytokine secretion, such as IL-1RA, IL-10, IL-12p70, IL-15, IL-8, and IL-23 in cells infected by both bacterial species. Furthermore, we also demonstrated that ROS production played a crucial role in controlling pyroptosis activation during B. pseudomallei infection in primary human monocytes. These findings suggested that pyroptosis induced by B. pseudomallei in the human monocytes may contribute to the pathogenesis of sepsis in acute melioidosis patients.
类鼻疽伯克霍尔德菌引起的类鼻疽病是一种死亡率很高的传染病。在急性类鼻疽病中，败血症是导致患者死亡的主要原因。一旦细菌进入血液，免疫系统就会失调，导致细胞因子风暴。与类鼻疽伯克霍尔德菌不同，一种密切相关但无毒力的菌株——泰国伯克霍尔德菌很少有报道称会导致患者发生细胞因子风暴或死亡。然而，强毒力的类鼻疽伯克霍尔德菌引起败血症的机制尚未完全阐明。有充分的文献记载表明，单核细胞在血液中细胞因子的产生中起着至关重要的作用。因此，本研究通过研究细胞焦亡这一已知在败血症中起关键作用的炎症性死亡途径，来确定原发性人单核细胞和 THP-1 单核细胞感染时，类鼻疽伯克霍尔德菌和泰国伯克霍尔德菌的固有免疫反应是否存在差异。我们的结果表明，尽管这两种细菌都具有相似的入侵人单核细胞的能力，但只有类鼻疽伯克霍尔德菌才能显著增加两种细胞类型胞质酶乳酸脱氢酶（LDH）的释放，以及半胱天冬酶-1 和 Gasdermin D 的激活。结果与细胞焦亡关键细胞因子白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）的显著增加一致。有趣的是，两种细菌感染的细胞中其他细胞因子的分泌，如白细胞介素-1受体拮抗剂（IL-1RA）、白细胞介素-10（IL-10）、白细胞介素-12p70（IL-12p70）、白细胞介素-15（IL-15）、白细胞介素-8（IL-8）和白细胞介素-23（IL-23），并没有显著差异。此外，我们还证明，活性氧（ROS）的产生在控制类鼻疽伯克霍尔德菌感染原发性人单核细胞时的细胞焦亡激活中起着至关重要的作用。这些发现表明，类鼻疽伯克霍尔德菌在人单核细胞中诱导的细胞焦亡可能导致急性类鼻疽病患者败血症的发病机制。
