Diniz Daniel G, de Oliveira Jhonnathan H P, Guerreiro Luma C F, de Menezes Gabriel C, de Assis Alexa C L, Duarte Tainá Q, Dos Santos Izabelly B D, Maciel Flávia D, Soares Gabrielly L da S, Araújo Sanderson C, Franco Felipe T de C, do Carmo Ediclei L, Morais Rafaela Dos A B, de Lima Camila M, Brites Dora, Anthony Daniel C, Diniz José A P, Diniz Cristovam W P
Laboratório de Investigações em Neurodegeneração e Infecção, Instituto de Ciências Biológicas, Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém 66073-005, Pará, Brazil.
Laboratório de Microscopia Eletrônica, Instituto Evandro Chagas, Belém 66077-830, Pará, Brazil.
Biomedicines. 2024 Jun 26;12(7):1420. doi: 10.3390/biomedicines12071420.
Our study investigated the innate immune response to 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 × 10 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 -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 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.
我们的研究通过评估小胶质细胞表型变化和疾病行为,作为眼内接种速殖子后炎症反应标志物,来研究对感染的先天免疫反应。使用相同的眼部途径和寄生虫负荷(2×10个速殖子),以生理盐水作为对照,将瑞士白化小鼠的疾病进展与先前记录的BALB/c小鼠的结果进行比较。与预期相反,瑞士白化小鼠表现出快速的致死性疾病进展,其特征为在感染后11 - 12天内出现明显的疾病行为和死亡,而幸存者没有明显的感染迹象。比较分析显示,感染的BALB/c小鼠对猫气味的回避减少,而感染的瑞士白化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,感染的瑞士白化小鼠齿状回分子层中的小胶质细胞有显著增加。层次聚类和判别分析确定了三个小胶质细胞形态簇,不同菌株的感染对其有不同影响。BALB/c小鼠的小胶质细胞分支和复杂性增加,而瑞士白化小鼠的小胶质细胞树突萎缩减少,形态复杂性降低。这些发现突出了疾病进展和炎症调节中的菌株特异性差异,表明炎症反应、耐受性和抗性存在谱系特异性机制。了解这些因素对于制定弓形虫病的控制措施至关重要。