Amity Institute of Biotechnology, Amity University Haryana, Manesar, Gurugram, India.
Clinical Microbiology and Infectious Diseases, Faculty of Health Sciences, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
PLoS One. 2022 Jul 14;17(7):e0270676. doi: 10.1371/journal.pone.0270676. eCollection 2022.
With a limited arsenal of available antifungal drugs and drug-resistance emergence, strategies that seek to reduce Candida immune evasion and virulence could be a promising alternative option. Harnessing metal homeostasis against C. albicans has gained wide prominence nowadays as a feasible antifungal strategy. Herein, the effect of magnesium (Mg) deprivation on the immune evasion mechanisms of C. albicans is demonstrated. We studied host pathogen interaction by using the THP-1 cell line model and explored the avenue that macrophage-mediated killing was enhanced under Mg deprivation, leading to altered cytokine (TNFα, IL-6 and IL10) production and reduced pyroptosis. Insights into the mechanisms revealed that hyphal damage inside the macrophage was diminished under Mg deprivation. Additionally, Mg deprivation led to cell wall remodelling; leading to enhanced β-1,3-glucan exposure, crucial for immune recognition, along with concomitant alterations in chitin and mannan levels. Furthermore, vacuole homeostasis was disrupted under Mg deprivation, as revealed by abrogated morphology and defective acidification of the vacuole lumen. Together, we demonstrated that Mg deprivation affected immune evasion mechanisms by: reduced hyphal damage, enhanced β-1,3-glucan exposure and altered vacuole functioning. The study establishes that Mg availability is indispensable for successful C. albicans immune evasion and specific Mg dependent pathways could be targeted for therapy.
由于现有的抗真菌药物种类有限，且出现了耐药性，因此，减少白色念珠菌免疫逃逸和毒力的策略可能是一种有前途的替代选择。利用金属稳态来对抗白色念珠菌已成为一种可行的抗真菌策略，目前备受关注。本文证明了镁（Mg）剥夺对白色念珠菌免疫逃逸机制的影响。我们使用 THP-1 细胞系模型研究了宿主-病原体相互作用，并探讨了在 Mg 剥夺下增强巨噬细胞介导的杀伤作用的途径，导致细胞因子（TNFα、IL-6 和 IL10）产生改变和细胞焦亡减少。对机制的深入了解表明，Mg 剥夺下巨噬细胞内的菌丝损伤减少。此外，Mg 剥夺导致细胞壁重塑，增强了β-1,3-葡聚糖的暴露，这对于免疫识别至关重要，同时伴随着几丁质和甘露聚糖水平的改变。此外，Mg 剥夺破坏了液泡稳态，表现为液泡形态破坏和液泡内腔酸化缺陷。综上所述，我们证明了 Mg 剥夺通过减少菌丝损伤、增强β-1,3-葡聚糖暴露和改变液泡功能来影响免疫逃逸机制。该研究表明，Mg 的可用性对于白色念珠菌成功的免疫逃逸是必不可少的，并且可以针对特定的 Mg 依赖性途径进行治疗。
