Department of Zoology, School of Natural Sciences, Trinity College Dublin, Dublin 2, Ireland.
School of Biological, Earth and Environmental Sciences, University College Cork, Cork, Ireland.
Parasit Vectors. 2019 Aug 14;12(1):402. doi: 10.1186/s13071-019-3655-9.
Ascariasis is a neglected tropical disease that affects 800 million people worldwide. Whereas most people only experience light worm burden, some people experience heavy worm burdens even after several rounds of chemotherapy, a phenomenon known as predisposition. Such heavy infections are associated with more severe symptoms and increased chronic morbidity.
In order to investigate potential mechanisms that may explain the observed predisposition, we infected mice with the porcine ascarid Ascaris suum using an established mouse model with two different mouse strains, where the C57BL/6J strain is more susceptible to infection and therefore a model for heavy infection and the CBA/Ca strain is more resistant and thus a model for light infection. At day 7 post-infection we investigated the liver proteome, using shotgun mass spectrometry, of both infected and control mice of each strain.
We identified intrinsic differences, between the two mouse strains, in both oxidative phosphorylation proteins and proteins involved in retinol metabolism. Additionally, we found differences between the two mouse strains in activation of the complement system, where the CBA/Ca strain has higher protein abundances for lectin pathway proteins and the C57BL/6J strain has higher protein abundances for complement inhibiting proteins. The CBA/Ca strain had a higher abundance of proteins involved in the activation of the complement cascade via the lectin pathway. In contrast, the C57BL/6J strain demonstrated a higher abundance of proteins involved in arresting the complement pathway.
We observed clear differences between the two mouse strains both intrinsically and under infection.
蛔虫病是一种被忽视的热带病，影响着全球 8 亿人。虽然大多数人只经历轻微的虫体负担，但有些人即使经过几轮化疗后仍会经历严重的虫体负担，这种现象被称为易感性。这种严重的感染与更严重的症状和增加的慢性发病率有关。
为了研究可能解释观察到的易感性的潜在机制，我们使用两种不同的小鼠品系，即用已建立的小鼠模型，用猪蛔虫感染小鼠，其中 C57BL/6J 品系更容易感染，因此是严重感染的模型，CBA/Ca 品系更具抗性，因此是轻度感染的模型。在感染后第 7 天，我们使用 shotgun 质谱法研究了两种感染和对照小鼠的肝蛋白质组。
我们发现，在两种小鼠品系之间，氧化磷酸化蛋白和视黄醇代谢蛋白都存在内在差异。此外，我们还发现两种小鼠品系在补体系统激活方面存在差异，其中 CBA/Ca 品系的凝集素途径蛋白的蛋白丰度更高，而 C57BL/6J 品系的补体抑制蛋白的蛋白丰度更高。CBA/Ca 品系中补体级联通过凝集素途径激活的蛋白丰度更高。相比之下，C57BL/6J 品系表现出更多参与补体途径阻滞的蛋白。
我们观察到两种小鼠品系在内在和感染方面都存在明显的差异。
