PMID- 34975868 OWN - NLM STAT- MEDLINE DCOM- 20220214 LR - 20220214 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - Systems Immunology Analyses Following Porcine Respiratory and Reproductive Syndrome Virus Infection and Vaccination. PG - 779747 LID - 10.3389/fimmu.2021.779747 [doi] LID - 779747 AB - This study was initiated to better understand the nature of innate immune responses and the relatively weak and delayed immune response against porcine reproductive and respiratory syndrome virus (PRRSV). Following modified live virus (MLV) vaccination or infection with two PRRSV-2 strains, we analyzed the transcriptome of peripheral blood mononuclear cells collected before and at three and seven days after vaccination or infection. We used blood transcriptional modules (BTMs)-based gene set enrichment analyses. BTMs related to innate immune processes were upregulated by PRRSV-2 strains but downregulated by MLV. In contrast, BTMs related to adaptive immune responses, in particular T cells and cell cycle, were downregulated by PRRSV-2 but upregulated by MLV. In addition, we found differences between the PRRSV strains. Only the more virulent strain induced a strong platelet activation, dendritic cell activation, interferon type I and plasma cell responses. We also calculated the correlations of BTM with the neutralizing antibody and the T-cell responses. Early downregulation (day 0-3) of dendritic cell and B-cell BTM correlated to both CD4 and CD8 T-cell responses. Furthermore, a late (day 3-7) upregulation of interferon type I modules strongly correlated to helper and regulatory T-cell responses, while inflammatory BTM upregulation correlated more to CD8 T-cell responses. BTM related to T cells had positive correlations at three days but negative associations at seven days post-infection. Taken together, this work contributes to resolve the complexity of the innate and adaptive immune responses against PRRSV and indicates a fundamentally different immune response to the less immunogenic MLV compared to field strains which induced robust adaptive immune responses. The identified correlates of T-cell responses will facilitate a rational approach to improve the immunogenicity of MLV. CI - Copyright (c) 2021 Bocard, Kick, Hug, Lischer, Kaser and Summerfield. FAU - Bocard, Loic Vivien AU - Bocard LV AD - Institute of Virology and Immunology, Mittelhausern, Switzerland. FAU - Kick, Andrew Robert AU - Kick AR AD - Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States. AD - Department of Chemistry & Life Science, United States Military Academy, West Point, NY, United States. FAU - Hug, Corinne AU - Hug C AD - Institute of Virology and Immunology, Mittelhausern, Switzerland. FAU - Lischer, Heidi Erika Lisa AU - Lischer HEL AD - Interfaculty Bioinformatics Unit, University of Bern, Bern, Switzerland. AD - Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland. FAU - Kaser, Tobias AU - Kaser T AD - Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States. FAU - Summerfield, Artur AU - Summerfield A AD - Institute of Virology and Immunology, Mittelhausern, Switzerland. AD - Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland. LA - eng PT - Journal Article DEP - 20211216 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Antibodies, Neutralizing) RN - 0 (Antibodies, Viral) RN - 0 (Interferon Type I) RN - 0 (Vaccines, Attenuated) RN - 0 (Viral Vaccines) SB - IM MH - Animals MH - Antibodies, Neutralizing/blood/immunology MH - Antibodies, Viral/blood/immunology MH - Gene Expression Profiling MH - Host-Pathogen Interactions/genetics/immunology MH - Immunogenicity, Vaccine MH - Interferon Type I/genetics/metabolism MH - Porcine Reproductive and Respiratory Syndrome/*immunology/prevention & control/virology MH - Porcine respiratory and reproductive syndrome virus/*immunology MH - Signal Transduction/genetics/immunology MH - Swine MH - T-Lymphocytes, Helper-Inducer/immunology/metabolism MH - T-Lymphocytes, Regulatory/immunology/metabolism MH - Up-Regulation/immunology MH - Vaccination/methods MH - Vaccines, Attenuated/administration & dosage/immunology MH - Viral Vaccines/administration & dosage/*immunology PMC - PMC8716554 OTO - NOTNLM OT - PRRSV (porcine reproductive and respiratory syndrome virus) OT - T-cell responses OT - innate response OT - systems immunology OT - transcriptomics COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/01/04 06:00 MHDA- 2022/02/15 06:00 PMCR- 2021/01/01 CRDT- 2022/01/03 05:38 PHST- 2021/09/19 00:00 [received] PHST- 2021/11/23 00:00 [accepted] PHST- 2022/01/03 05:38 [entrez] PHST- 2022/01/04 06:00 [pubmed] PHST- 2022/02/15 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2021.779747 [doi] PST - epublish SO - Front Immunol. 2021 Dec 16;12:779747. doi: 10.3389/fimmu.2021.779747. eCollection 2021.