The comprehensive transcriptomic atlas of porcine immune tissues and the peripheral blood mononuclear cell (PBMC) immune dynamics reveal core immune genes.

Background: Viral diseases have profoundly influenced the sustainable development of the swine farming industry. With the development of genomics technology, the combination of transcriptome, genetic variation, immune response, and QTL mapping data to illustrate the interactions between pathogen and host immune system, will be an effective tool for identification of disease resistance genes in pigs. The immune system of an organism is the source of disease resistance in livestock, consisting of various immune tissues, as well as the immune cells and cytokines they produced. However, comprehensive systematic studies on transcriptome of porcine immune tissues are still rare. Poly(I:C), as a viral mimic, is commonly used to study immune responses of the body during viral infections, and serves as a valuable tool for investigating immune mechanisms in swine.

Results: WGCNA analysis identified core immune genes across six immune tissues (bone marrow, jejunum, lymph node, PBMC, spleen, thymus) in Landrace pigs, which are also crucial for the development of PBMCs. The examination of the changes in the proportion of immune cells during three developmental stages (1-month-old, 4-month-old, 7-month-old) shows a shift from innate immunity to humoral immunity. By integrating different epigenetic genomics datasets, we identified several core immune genes and their causal variants, including IFI44, IFIT5, EIF2AK2 and others, which are closely related to immune development and response. Functional validation studies reveal that the IFI44 gene acts as a negative regulator of the antiviral response; its inhibition effect significantly reduced Poly(I:C)-induced cell necrosis, while enhancing apoptosis to combat viral infections.

Conclusion: Our study elucidated the fundamental transcriptional program in porcine immune tissues and the immunodynamics underlying development of PBMCs, identifying many core immune genes, including IFI44, which plays a critical negative regulator role in the antiviral response, providing valuable insights for breeding programs aimed at enhancing pig disease resistance.