Cargando…
Integrated time-series transcriptomic and metabolomic analyses reveal different inflammatory and adaptive immune responses contributing to host resistance to PRRSV
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 PRR...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631489/ https://www.ncbi.nlm.nih.gov/pubmed/36341362 http://dx.doi.org/10.3389/fimmu.2022.960709 |
_version_ | 1784823829332230144 |
---|---|
author | Wu, Qingqing Han, Yu Wu, Xianmeng Wang, Yuan Su, Qiuju Shen, Yang Guan, Kaifeng Michal, Jennifer J. Jiang, Zhihua Liu, Bang Zhou, Xiang |
author_facet | Wu, Qingqing Han, Yu Wu, Xianmeng Wang, Yuan Su, Qiuju Shen, Yang Guan, Kaifeng Michal, Jennifer J. Jiang, Zhihua Liu, Bang Zhou, Xiang |
author_sort | Wu, Qingqing |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9631489 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96314892022-11-04 Integrated time-series transcriptomic and metabolomic analyses reveal different inflammatory and adaptive immune responses contributing to host resistance to PRRSV Wu, Qingqing Han, Yu Wu, Xianmeng Wang, Yuan Su, Qiuju Shen, Yang Guan, Kaifeng Michal, Jennifer J. Jiang, Zhihua Liu, Bang Zhou, Xiang Front Immunol Immunology 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. Frontiers Media S.A. 2022-10-20 /pmc/articles/PMC9631489/ /pubmed/36341362 http://dx.doi.org/10.3389/fimmu.2022.960709 Text en Copyright © 2022 Wu, Han, Wu, Wang, Su, Shen, Guan, Michal, Jiang, Liu and Zhou https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Wu, Qingqing Han, Yu Wu, Xianmeng Wang, Yuan Su, Qiuju Shen, Yang Guan, Kaifeng Michal, Jennifer J. Jiang, Zhihua Liu, Bang Zhou, Xiang Integrated time-series transcriptomic and metabolomic analyses reveal different inflammatory and adaptive immune responses contributing to host resistance to PRRSV |
title | Integrated time-series transcriptomic and metabolomic analyses reveal different inflammatory and adaptive immune responses contributing to host resistance to PRRSV |
title_full | Integrated time-series transcriptomic and metabolomic analyses reveal different inflammatory and adaptive immune responses contributing to host resistance to PRRSV |
title_fullStr | Integrated time-series transcriptomic and metabolomic analyses reveal different inflammatory and adaptive immune responses contributing to host resistance to PRRSV |
title_full_unstemmed | Integrated time-series transcriptomic and metabolomic analyses reveal different inflammatory and adaptive immune responses contributing to host resistance to PRRSV |
title_short | Integrated time-series transcriptomic and metabolomic analyses reveal different inflammatory and adaptive immune responses contributing to host resistance to PRRSV |
title_sort | integrated time-series transcriptomic and metabolomic analyses reveal different inflammatory and adaptive immune responses contributing to host resistance to prrsv |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631489/ https://www.ncbi.nlm.nih.gov/pubmed/36341362 http://dx.doi.org/10.3389/fimmu.2022.960709 |
work_keys_str_mv | AT wuqingqing integratedtimeseriestranscriptomicandmetabolomicanalysesrevealdifferentinflammatoryandadaptiveimmuneresponsescontributingtohostresistancetoprrsv AT hanyu integratedtimeseriestranscriptomicandmetabolomicanalysesrevealdifferentinflammatoryandadaptiveimmuneresponsescontributingtohostresistancetoprrsv AT wuxianmeng integratedtimeseriestranscriptomicandmetabolomicanalysesrevealdifferentinflammatoryandadaptiveimmuneresponsescontributingtohostresistancetoprrsv AT wangyuan integratedtimeseriestranscriptomicandmetabolomicanalysesrevealdifferentinflammatoryandadaptiveimmuneresponsescontributingtohostresistancetoprrsv AT suqiuju integratedtimeseriestranscriptomicandmetabolomicanalysesrevealdifferentinflammatoryandadaptiveimmuneresponsescontributingtohostresistancetoprrsv AT shenyang integratedtimeseriestranscriptomicandmetabolomicanalysesrevealdifferentinflammatoryandadaptiveimmuneresponsescontributingtohostresistancetoprrsv AT guankaifeng integratedtimeseriestranscriptomicandmetabolomicanalysesrevealdifferentinflammatoryandadaptiveimmuneresponsescontributingtohostresistancetoprrsv AT michaljenniferj integratedtimeseriestranscriptomicandmetabolomicanalysesrevealdifferentinflammatoryandadaptiveimmuneresponsescontributingtohostresistancetoprrsv AT jiangzhihua integratedtimeseriestranscriptomicandmetabolomicanalysesrevealdifferentinflammatoryandadaptiveimmuneresponsescontributingtohostresistancetoprrsv AT liubang integratedtimeseriestranscriptomicandmetabolomicanalysesrevealdifferentinflammatoryandadaptiveimmuneresponsescontributingtohostresistancetoprrsv AT zhouxiang integratedtimeseriestranscriptomicandmetabolomicanalysesrevealdifferentinflammatoryandadaptiveimmuneresponsescontributingtohostresistancetoprrsv |