Ruedas-Torres, InésRodríguez-Gómez, Irene M.Sánchez-Carvajal, José MaríaGuil-Luna, SilviaLarenas-Muñoz, FernandaPallarés, Francisco J.Carrasco, LibradoGómez-Laguna, Jaime2022-07-262022-07-262021-05-11Ruedas-Torres I, Rodríguez-Gómez IM, Sánchez-Carvajal JM, Guil-Luna S, Larenas-Muñoz F, Pallarés FJ, et al. Up-Regulation of Immune Checkpoints in the Thymus of PRRSV-1-Infected Piglets in a Virulence-Dependent Fashion. Front Immunol. 2021 May 11;12:671743http://hdl.handle.net/10668/3823Virulent porcine reproductive and respiratory syndrome virus (PRRSV) strains, such as the Lena strain, have demonstrated a higher thymus tropism than low virulent strains. Virulent PRRSV strains lead to severe thymus atrophy, which could be related to marked immune dysregulation. Impairment of T-cell functions through immune checkpoints has been postulated as a strategy executed by PRRSV to subvert the immune response, however, its role in the thymus, a primary lymphoid organ, has not been studied yet. Therefore, the goal of this study was to evaluate the expression of selected immune checkpoints (PD1/PDL1, CTLA4, TIM3, LAG3, CD200R1 and IDO1) in the thymus of piglets infected with two different PRRSV-1 strains. Thymus samples from piglets infected with the low virulent 3249 strain, the virulent Lena strain and mock-infected were collected at 1, 3, 6, 8 and 13 days post-infection (dpi) to analyze PRRSV viral load, relative quantification and immunohistochemical staining of immune checkpoints. PD1/PDL1, CTLA4, TIM3, LAG3 and IDO1 immune checkpoints were significantly up-regulated in the thymus of PRRSV infected piglets, especially in those infected with the virulent Lena strain from 6 dpi onwards. This up-regulation was associated with disease progression, high viral load and cell death. Co-expression of these molecules can affect T-cell development, maturation and selection, negatively regulating the host immune response against PRRSV.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Immune checkpointsThymusImmunosuppressionT-cell exhaustionPRRSVTimoInmunosupresiónLinfocitos TVirus del síndrome respiratorio y reproductivo porcinoMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Diseases::Animal Diseases::Swine Diseases::Porcine Reproductive and Respiratory SyndromeMedical Subject Headings::Organisms::Viruses::Vertebrate Viruses::RNA Viruses::Nidovirales::Arteriviridae::Arterivirus::Porcine respiratory and reproductive syndrome virusMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Artiodactyla::SwineMedical Subject Headings::Anatomy::Tissues::Lymphoid Tissue::Thymus GlandMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Chemical Processes::Biochemical Processes::Up-RegulationMedical Subject Headings::Phenomena and Processes::Microbiological Phenomena::VirulenceMedical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Antigens, Differentiation::Antigens, Differentiation, T-Lymphocyte::CTLA-4 AntigenMedical Subject Headings::Phenomena and Processes::Microbiological Phenomena::Virus Physiological Phenomena::Viral LoadMedical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-LymphocytesMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Deathresearch article34046040Acceso abierto10.3389/fimmu.2021.6717431664-3224PMC8144631