Up-Regulation of Immune Checkpoints in the Thymus of PRRSV-1-Infected Piglets in a Virulence-Dependent Fashion

Autor: Jaime Gómez-Laguna, F. Larenas-Muñoz, Irene M. Rodríguez-Gómez, Inés Ruedas-Torres, Jose María Sánchez-Carvajal, Librado Carrasco, Silvia Guil-Luna, F.J. Pallarés
Přispěvatelé: [Ruedas-Torres,I, Rodríguez-Gómez,IM, Sánchez-Carvajal,JM, Larenas-Muñoz,F, Pallarés,FJ, Carrasco,L, Gómez-Laguna,J] Department of Anatomy and Comparative Pathology and Toxicology, International Agrifood, Faculty of Veterinary Medicine, University of Córdoba, Córdoba, Spain. [Guil-Luna,S] Maimónides Institute for Biomedical Research of Córdoba, IMIBIC, Córdoba, Spain., JG-L is supported by a 'Ramón y Cajal' contract of the Spanish Ministry of Economy and Competitiveness (RYC-2014-16735). This work was supported by the Spanish Ministry of Economy and Competitiveness (#AGL2016-76111-R and PID2019-109718GB-I00).
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Phenomena and Processes::Microbiological Phenomena::Virulence [Medical Subject Headings]
LAG3
Swine
viruses
animal diseases
Immunology
Porcine Reproductive and Respiratory Syndrome
Virulence
chemical and pharmacologic phenomena
Thymus Gland
medicine.disease_cause
Inmunosupresión
Immune system
thymus
Anatomy::Tissues::Lymphoid Tissue::Thymus Gland [Medical Subject Headings]
T-cell exhaustion
Diseases::Animal Diseases::Swine Diseases::Porcine Reproductive and Respiratory Syndrome [Medical Subject Headings]
Organisms::Eukaryota::Animals [Medical Subject Headings]
Phenomena and Processes::Chemical Phenomena::Chemical Processes::Biochemical Processes::Up-Regulation [Medical Subject Headings]
medicine
Immunology and Allergy
Animals
Chemicals and Drugs::Biological Factors::Antigens::Antigens
Surface::Antigens
Differentiation::Antigens
Differentiation
T-Lymphocyte::CTLA-4 Antigen [Medical Subject Headings]

Porcine respiratory and reproductive syndrome virus
Tropism
Original Research
Phenomena and Processes::Microbiological Phenomena::Virus Physiological Phenomena::Viral Load [Medical Subject Headings]
Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes
Mononuclear::Lymphocytes::T-Lymphocytes [Medical Subject Headings]

immunosuppression
biology
virus diseases
Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Artiodactyla::Swine [Medical Subject Headings]
Linfocitos T
RC581-607
Immune dysregulation
immune checkpoints
Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death [Medical Subject Headings]
Porcine reproductive and respiratory syndrome virus
biology.organism_classification
Virology
Up-Regulation
Lymphatic system
PRRSV
Virus del síndrome respiratorio y reproductivo porcino
Timo
Organisms::Viruses::Vertebrate Viruses::RNA Viruses::Nidovirales::Arteriviridae::Arterivirus::Porcine respiratory and reproductive syndrome virus [Medical Subject Headings]
Immunologic diseases. Allergy
Viral load
Zdroj: Frontiers in Immunology
Frontiers in Immunology, Vol 12 (2021)
Popis: Virulent 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.
Databáze: OpenAIRE