Integrated time-series transcriptomic and metabolomic analyses reveal different inflammatory and adaptive immune responses contributing to host resistance to PRRSV

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious disease that affects the global pig industry. To understand mechanisms of susceptibility/resistance to PRRSV, this study profiled the time-serial white blood cells transcriptomic and serum metabolomic responses to PRRSV in piglets from a crossbred population of PRRSV-resistant Tongcheng pigs and PRRSV-susceptible Large White pigs. Gene set enrichment analysis (GSEA) illustrated that PRRSV infection up-regulated the expression levels of marker genes of dendritic cells, monocytes and neutrophils and inflammatory response, but down-regulated T cells, B cells and NK cells markers. CIBERSORT analysis confirmed the higher T cells proportion in resistant pigs during PRRSV infection. Resistant pigs showed a significantly higher level of T cell activation and lower expression levels of monocyte surface signatures post infection than susceptible pigs, corresponding to more severe suppression of T cell immunity and inflammatory response in susceptible pigs. Differentially expressed genes between resistant/susceptible pigs during the course of infection were significantly enriched in oxidative stress, innate immunity and humoral immunity, cell cycle, biotic stimulated cellular response, wounding response and behavior related pathways. Fourteen of these genes were distributed in 5 different QTL regions associated with PRRSV-related traits. Chemokine CXCL10 levels post PRRSV infection were differentially expressed between resistant pigs and susceptible pigs and can be a promising marker for susceptibility/resistance to PRRSV. Furthermore, the metabolomics dataset indicated differences in amino acid pathways and lipid metabolism between pre-infection/post-infection and resistant/susceptible pigs. The majority of metabolites levels were also down-regulated after PRRSV infection and were significantly positively correlated to the expression levels of marker genes in adaptive immune response. The integration of transcriptome and metabolome revealed concerted molecular events triggered by the infection, notably involving inflammatory response, adaptive immunity and G protein-coupled receptor downstream signaling. This study has increased our knowledge of the immune response differences induced by PRRSV infection and susceptibility differences at the transcriptomic and metabolomic levels, providing the basis for the PRRSV resistance mechanism and effective PRRS control.

Integrative transcriptomic profiling of mRNA, miRNA, circRNA, and lncRNA in alveolar macrophages isolated from PRRSV-infected porcine

“…The exploration of antibodies or inhibitors aimed at CTLA4 has shown encouraging results in cancer treatment ( 57 ). PRRSV, noted for its immunosuppressive character, has been implicated in the inadequate activation of T cells ( 58 ). In the present study, CTLA4 emerged as a top one ranking mRNA in ceRNA network ( Figure 7 ), suggesting a significant role in PRRSV pathogenesis.…”

Progress in PRRSV Infection and Adaptive Immune Response Mechanisms

“…The adaptive immune response includes T cell-mediated cellular immunity (CMI) and humoral immunity (HI), with specific antibody production by effector B cells. Inflammatory responses, dendritic cells, monocytes, and neutrophil marker gene expression levels were shown to be elevated by PRRSV infection using gene set enrichment analysis, while T cells, B cells, and NK cell-related gene markers were downregulated [ 45 ].…”

RNA-Seq Analysis of Peripheral Whole Blood from Dairy Bulls with High and Low Antibody-Mediated Immune Responses—A Preliminary Study

“…Therefore, identifying DEGs related to immune responses is crucial for explaining and understanding genetic variations in disease prevention and diagnosis [17,18] and may help improve the immunity of animals. In this study, utilizing the whole blood transcriptome of dairy bulls classified as high-and low-AMIR groups, we aimed to (1) identify DEGs associ-ated with the adaptive immune response in cattle; (2) study the key signaling pathways of the immune response and the changes of various regulatory molecules, thus elucidating the immunomodulatory mechanisms related to disease resistance in dairy cattle and providing new insights for improving animal health and welfare from an immunological perspective.…”