Differentially expressed genes in the blood, spleen, and liver of Peromyscus leucopus and Mus musculus with or without treatment with lipopolysaccharide

Animals that are competent reservoirs of zoonotic pathogens commonly
suffer little morbidity from the infections. To investigate mechanisms of
this tolerance of infection, we used single-dose lipopolysaccharide (LPS)
as an experimental model of inflammation and compared the responses by two
rodents: Peromyscus leucopus, white-footed deermouse and reservoir for
agents of Lyme disease and other zoonoses, and the house mouse Mus
musculus. Four hours after injection with LPS or saline, blood, spleen and
liver samples were collected and subjected to RNA-seq, metabolomics, and
specific RT-qPCR. Differential expression analysis was at gene, pathway,
and network levels. LPS-treated deermice showed similar signs of sickness
as exposed mice and had similar increases in corticosterone levels and
expression of interleukin (IL)-6, tumor necrosis factor, IL-1beta, and
C-reactive protein. By network analysis the M. musculus response to LPS
was characterized as cytokine-associated, while the P. leucopus response
was dominated by neutrophil activity terms. In addition, dichotomies in
expression of arginase 1 and nitric oxide synthase 2 and of IL-10 and
IL-12 were consistent with type M1 macrophage responses in mice and type
M2 in deermice. This dataset comprises the list of differentially
expressed genes from the RNA-seq analysis of 20 P. leucopus (10 females
and 10 males) and 20 M. musculus (10 females and 10 males) that were
inoculated intraperitoneally with 10 mg/kg of E. coli lipopolysaccharide
(6 females and 6 males of each species) or with saline alone (4 females or
4 males of each species) at time 0 and then the animals were euthanized at
4 hours. The tissues were then processed for RNA extraction, cDNA library
preparations, and sequencing and then analysis as described under
Methods.

作为人畜共患病病原体合格储存宿主的动物，通常在感染后几乎无明显发病症状。为探究这种感染耐受的内在机制，我们以单剂量脂多糖（lipopolysaccharide, LPS）作为炎症实验模型，对比了两种啮齿类动物的免疫应答：白足鼠（Peromyscus leucopus）——莱姆病及其他人畜共患病病原体的储存宿主——以及小家鼠（Mus musculus）。在向两组动物分别注射LPS或生理盐水4小时后，采集血液、脾脏与肝脏样本，进行RNA测序（RNA-seq）、代谢组学以及特异性反转录实时定量PCR（RT-qPCR）检测。差异表达分析分别在基因、通路及网络层面展开。经LPS处理的白足鼠与注射LPS的小家鼠表现出相似的患病体征，其皮质酮水平以及白细胞介素-6（IL-6）、肿瘤坏死因子、IL-1β以及C反应蛋白（C-reactive protein）的表达量均出现类似幅度的升高。通过网络分析发现，小家鼠对LPS的应答以细胞因子相关通路为主要特征，而白足鼠的应答则以中性粒细胞活性相关术语为主导。此外，精氨酸酶1与一氧化氮合酶2、IL-10与IL-12的表达呈现出截然相反的模式，这与小家鼠的M1型巨噬细胞应答以及白足鼠的M2型巨噬细胞应答特征相符。本数据集包含了对20只白足鼠（10只雌性、10只雄性）与20只小家鼠（10只雌性、10只雄性）进行RNA测序分析后得到的差异表达基因列表。所有受试动物于0时刻经腹腔注射10 mg/kg大肠杆菌脂多糖（每组各6只雌性、6只雄性），或仅注射生理盐水（每组各4只雌性、4只雄性），并于注射后4小时实施安乐死。随后按照“方法”部分所述流程，对组织进行RNA提取、cDNA文库构建及测序分析。