Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
School of Dentistry, King Mongkut's Institute of Technology Ladkrabang, Bangkok, Thailand.
PLoS One. 2023 Feb 9;18(2):e0280944. doi: 10.1371/journal.pone.0280944. eCollection 2023.
Melioidosis is an infectious disease with high mortality rates in human, caused by the bacterium Burkholderia pseudomallei. As an intracellular pathogen, B. pseudomallei can escape from the phagosome and induce multinucleated giant cells (MNGCs) formation resulting in antibiotic resistance and immune evasion. A novel strategy to modulate host response against B. pseudomallei pathogenesis is required. In this study, an active metabolite of vitamin D3 (1α,25-dihydroxyvitamin D3 or 1α,25(OH)2D3) was selected to interrupt pathogenesis of B. pseudomallei in a human lung epithelium cell line, A549. The results demonstrated that pretreatment with 10-6 M 1α,25(OH)2D3 could reduce B. pseudomallei internalization to A549 cells at 4 h post infection (P < 0.05). Interestingly, the presence of 1α,25(OH)2D3 gradually reduced MNGC formation at 8, 10 and 12 h compared to that of the untreated cells (P < 0.05). Furthermore, pretreatment with 10-6 M 1α,25(OH)2D3 considerably increased hCAP-18/LL-37 mRNA expression (P < 0.001). Additionally, pro-inflammatory cytokines, including MIF, PAI-1, IL-18, CXCL1, CXCL12 and IL-8, were statistically decreased (P < 0.05) in 10-6 M 1α,25(OH)2D3-pretreated A549 cells by 12 h post-infection. Taken together, this study indicates that pretreatment with 10-6 M 1α,25(OH)2D3 has the potential to reduce the internalization of B. pseudomallei into host cells, decrease MNGC formation and modulate host response during B. pseudomallei infection by minimizing the excessive inflammatory response. Therefore, 1α,25(OH)2D3 supplement may provide an effective supportive treatment for melioidosis patients to combat B. pseudomallei infection and reduce inflammation in these patients.
类鼻疽是一种人类高死亡率的传染病，由伯克霍尔德菌引起。作为一种细胞内病原体，B. pseudomallei 可以从吞噬体中逃逸，并诱导多核巨细胞（MNGCs）的形成，导致抗生素耐药和免疫逃逸。因此，需要一种新的策略来调节宿主对 B. pseudomallei 发病机制的反应。在这项研究中，选择维生素 D3 的一种活性代谢物（1α,25-二羟维生素 D3 或 1α,25(OH)2D3）来打断人类肺上皮细胞系 A549 中 B. pseudomallei 的发病机制。结果表明，感染后 4 小时用 10-6 M 1α,25(OH)2D3 预处理可减少 B. pseudomallei 进入 A549 细胞（P < 0.05）。有趣的是，与未处理的细胞相比，1α,25(OH)2D3 的存在逐渐减少了 8、10 和 12 小时时多核巨细胞的形成（P < 0.05）。此外，10-6 M 1α,25(OH)2D3 预处理可显著增加 hCAP-18/LL-37 mRNA 的表达（P < 0.001）。此外，感染后 12 小时，炎性细胞因子 MIF、PAI-1、IL-18、CXCL1、CXCL12 和 IL-8 的水平在 10-6 M 1α,25(OH)2D3 预处理的 A549 细胞中显著降低（P < 0.05）。总之，本研究表明，10-6 M 1α,25(OH)2D3 预处理可减少 B. pseudomallei 进入宿主细胞，减少多核巨细胞的形成，并通过减轻过度炎症反应来调节 B. pseudomallei 感染期间的宿主反应。因此，1α,25(OH)2D3 补充可能为类鼻疽患者提供有效的支持性治疗，以对抗 B. pseudomallei 感染并减轻这些患者的炎症。
