关键词: Toxoplasma gondii dentate gyrus microglia ocular infection resistance sickness behavior tolerance

来  源:   DOI:10.3390/biomedicines12071420   PDF(Pubmed)

Abstract:
Our study investigated the innate immune response to Toxoplasma gondii infection by assessing microglial phenotypic changes and sickness behavior as inflammatory response markers post-ocular tachyzoite instillation. Disease progression in Swiss albino mice was compared with the previously documented outcomes in BALB/c mice using an identical ocular route and parasite burden (2 × 105 tachyzoites), with saline as the control. Contrary to expectations, the Swiss albino mice displayed rapid, lethal disease progression, marked by pronounced sickness behaviors and mortality within 11-12 days post-infection, while the survivors exhibited no apparent signs of infection. Comparative analysis revealed the T. gondii-infected BALB/c mice exhibited reduced avoidance of feline odors, while the infected Swiss albino mice showed enhanced avoidance responses. There was an important increase in microglial cells in the dentate gyrus molecular layer of the infected Swiss albino mice compared to the BALB/c mice and their respective controls. Hierarchical cluster and discriminant analyses identified three microglial morphological clusters, differentially affected by T. gondii infection across strains. The BALB/c mice exhibited increased microglial branching and complexity, while the Swiss albino mice showed reduced shrunken microglial arbors, diminishing their morphological complexity. These findings highlight strain-specific differences in disease progression and inflammatory regulation, indicating lineage-specific mechanisms in inflammatory responses, tolerance, and resistance. Understanding these elements is critical in devising control measures for toxoplasmosis.
摘要:
我们的研究通过评估小胶质细胞表型变化和疾病行为作为眼部速殖子滴注后的炎症反应标志物,研究了对弓形虫感染的先天免疫反应。将瑞士白化病小鼠的疾病进展与先前记录的BALB/c小鼠使用相同的眼部途径和寄生虫负担(2×105速殖子)的结果进行了比较,用盐水作为对照。与预期相反,瑞士白化病小鼠表现得很快,致命的疾病进展,感染后11-12天内明显的疾病行为和死亡率,而幸存者没有表现出明显的感染迹象。比较分析显示,感染弓形虫的BALB/c小鼠对猫科动物气味的回避减少,而受感染的瑞士白化病小鼠表现出增强的回避反应。与BALB/c小鼠及其各自的对照相比,受感染的瑞士白化病小鼠的齿状回分子层中的小胶质细胞显着增加。分层聚类和判别分析确定了三个小胶质细胞形态簇,不同菌株受弓形虫感染的影响。BALB/c小鼠表现出增加的小胶质细胞分支和复杂性,而瑞士白化病小鼠的小胶质细胞萎缩减少,减少它们的形态复杂性。这些发现强调了疾病进展和炎症调节的菌株特异性差异,表明炎症反应中的谱系特异性机制,容忍度,和阻力。了解这些要素对于制定弓形虫病的控制措施至关重要。
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