An Exaggerated Immune Response in Female BALB/c Mice Controls Initial Toxoplasma gondii Multiplication but Increases Mortality and Morbidity Relative to Male Mice.
An Exaggerated Immune Response in Female BALB/c Mice Controls Initial Toxoplasma gondii Multiplication but Increases Mortality and Morbidity Relative to Male Mice.
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DOI：
10.3390/pathogens10091154
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发表时间：
2021-09-08
期刊：
影响因子：
--
通讯作者：
Roberts CW
中科院分区：
文献类型：
--
作者：
Alonaizan R;Woods S;Hargrave KE;Roberts CW
研究表明，雌性小鼠更容易受到弓形虫感染，其死亡率比雄性小鼠更高。然而，这是否是由于无法控制最初的寄生虫繁殖或由于免疫系统的有害影响尚未确定。因此，进行了以下研究来确定性别对弓形虫感染期间早期寄生虫增殖和免疫反应的影响，并将其与疾病结果相关联。通过应用体内成像系统（IVIS）和表达弓形虫的荧光素酶来研究早期寄生虫的复制。同时通过细胞计数珠阵列研究免疫学事件以量化关键的免疫介质。结果证实了之前的发现，即雌性小鼠比雄性小鼠更容易受到急性感染，这是因为其死亡率和体重减轻较高。然而，与预期相矛盾的是，雌性小鼠在急性感染期间的寄生虫负担低于雄性小鼠。与雄性小鼠相比，雌性小鼠的单核细胞趋化蛋白-1 (MCP-1)、干扰素 (IFN)-γ 和肿瘤坏死因子 (TNF)-α 的产量也显着增加。发现 MCP-1 由弓形虫以剂量依赖性方式诱导，这表明在雌性小鼠中检测到的水平增加是由于宿主介导的性别差异而不是由于寄生虫负载所致。然而，MCP-1 不受雌激素或睾酮生理浓度的影响，表明体内观察到的两性之间的 MCP-1 差异是由于尚未确定的中间因素造成的，该因素反过来影响 MCP-1 水平。这些结果表明，与雄性小鼠相比，雌性小鼠更强的免疫反应增强了它们控制寄生虫复制的能力，但增加了它们的发病率和死亡率。
Studies indicate that female mice are more susceptible to T. gondii infection, as defined by higher mortality rates in comparison to male mice. However, whether this is due to an inability to control initial parasite multiplication or due to detrimental effects of the immune system has not been determined. Therefore, the following studies were undertaken to determine the influence of sex on early parasite multiplication and the immune response during T. gondii infection and to correlate this with disease outcome. Early parasite replication was studied through applying an in vivo imaging system (IVIS) with luciferase expressing T. gondii. In parallel immunological events were studied by cytometric bead array to quantify key immunological mediators. The results confirmed the previous findings that female mice are more susceptible to acute infection, as determined by higher mortality rates and weight loss compared with males. However, conflicting with expectations, female mice had lower parasite burdens during the acute infection than male mice. Female mice also exhibited significantly increased production of Monocyte Chemoattractant Protein-1 (MCP-1), Interferon (IFN)-γ, and Tumour Necrosis Factor (TNF)-α than male mice. MCP-1 was found to be induced by T. gondii in a dose dependent manner suggesting that the observed increased levels detected in female mice was due to a host-mediated sex difference rather than due to parasite load. However, MCP-1 was not affected by physiological concentration of estrogen or testosterone, indicating that MCP-1 differences observed between the sexes in vivo are due to an as yet unidentified intermediary factor that in turn influences MCP-1 levels. These results suggest that a stronger immune response in female mice compared with male mice enhances their ability to control parasite replication but increases their morbidity and mortality.
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影响因子：
4
作者：
Weiss LM;Dubey JP
通讯作者：
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影响因子：
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作者：
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作者：
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