Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture & National Engineering Laboratory for Animal Breeding, College of Animal Science and Technologyn, China Agricultural University, Beijing, 100193, China.
Dabei-Nong Science and Technology Group Co., Ltd, Beijing, 100080, China.
BMC Genomics. 2024 Jul 25;25(1):719. doi: 10.1186/s12864-024-10603-9.
Pigs serve as a crucial source of protein in the human diet and play a fundamental role in ensuring food security. However, infectious diseases caused by bacteria or viruses are a major threat to effective global pig farming, jeopardizing human health. Peripheral blood mononuclear cells (PBMCs) are a mixture of immune cells that play crucial roles in immunity and disease resistance in pigs. Previous studies on the gene expression regulation patterns of PBMCs have concentrated on a single immune stimulus or immune cell subpopulation, which has limited our comprehensive understanding of the mechanisms of the pig immune response.
Here, we integrated and re-analyzed RNA-seq data published online for porcine PBMC stimulated by lipopolysaccharide (LPS), polyinosinic acid (PolyI:C), and various unknown microorganisms (EM). The results revealed that gene expression and its functional characterization are highly specific to the pathogen, identifying 603, 254, and 882 pathogen-specific genes and 38 shared genes, respectively. Notably, LPS and PolyI:C stimulation directly triggered inflammatory and immune-response pathways, while exposure to mixed microbes (EM) enhanced metabolic processes. These pathogen-specific genes were enriched in immune trait-associated quantitative trait loci (QTL) and eGenes in porcine immune tissues and were implicated in specific cell types. Furthermore, we discussed the roles of eQTLs rs3473322705 and rs1109431654 in regulating pathogen- and cell-specific genes CD300A and CD93, using cellular experiments. Additionally, by integrating genome-wide association studies datasets from 33 complex traits and diseases in humans, we found that pathogen-specific genes were significantly enriched for immune traits and metabolic diseases.
We systematically analyzed the gene expression profiles of the three stimulations and demonstrated pathogen-specific and cell-specific gene regulation across different stimulations in porcine PBMCs. These findings enhance our understanding of shared and distinct regulatory mechanisms of genetic variants in pig immune traits.
猪是人类饮食中重要的蛋白质来源，对保障食品安全起着至关重要的作用。然而，细菌或病毒引起的传染病是全球有效养猪的主要威胁，危及人类健康。外周血单核细胞（PBMC）是免疫细胞的混合物，在猪的免疫和疾病抵抗中起着关键作用。之前关于 PBMC 基因表达调控模式的研究集中在单一的免疫刺激或免疫细胞亚群上，这限制了我们对猪免疫反应机制的全面理解。
在这里，我们整合并重新分析了在线发表的猪 PBMC 受脂多糖（LPS）、聚肌苷酸（PolyI:C）和各种未知微生物（EM）刺激的 RNA-seq 数据。结果表明，基因表达及其功能特征与病原体高度特异，分别鉴定出 603、254 和 882 个病原体特异基因和 38 个共享基因。值得注意的是，LPS 和 PolyI:C 刺激直接触发了炎症和免疫反应途径，而暴露于混合微生物（EM）增强了代谢过程。这些病原体特异基因在猪免疫组织中的免疫性状相关数量性状位点（QTL）和 eGenes 中富集，并与特定细胞类型相关。此外，我们通过细胞实验讨论了 eQTLs rs3473322705 和 rs1109431654 对调节病原体和细胞特异基因 CD300A 和 CD93 的作用。此外，通过整合来自人类 33 种复杂性状和疾病的全基因组关联研究数据集，我们发现病原体特异基因在免疫性状和代谢疾病方面显著富集。
我们系统地分析了三种刺激的基因表达谱，证明了猪 PBMC 中不同刺激下病原体特异和细胞特异基因的调节。这些发现增强了我们对猪免疫性状中遗传变异共享和独特调节机制的理解。
