PMID- 34046040
OWN - NLM
STAT- MEDLINE
DCOM- 20211018
LR  - 20211018
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - Up-Regulation of Immune Checkpoints in the Thymus of PRRSV-1-Infected Piglets in 
      a Virulence-Dependent Fashion.
PG  - 671743
LID - 10.3389/fimmu.2021.671743 [doi]
LID - 671743
AB  - 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.
CI  - Copyright (c) 2021 Ruedas-Torres, Rodriguez-Gomez, Sanchez-Carvajal, Guil-Luna, 
      Larenas-Munoz, Pallares, Carrasco and Gomez-Laguna.
FAU - Ruedas-Torres, Ines
AU  - Ruedas-Torres I
AD  - Department of Anatomy and Comparative Pathology and Toxicology, International 
      Agrifood Campus of Excellence (ceiA3), Faculty of Veterinary Medicine, University 
      of Cordoba, Cordoba, Spain.
FAU - Rodriguez-Gomez, Irene M
AU  - Rodriguez-Gomez IM
AD  - Department of Anatomy and Comparative Pathology and Toxicology, International 
      Agrifood Campus of Excellence (ceiA3), Faculty of Veterinary Medicine, University 
      of Cordoba, Cordoba, Spain.
FAU - Sanchez-Carvajal, Jose Maria
AU  - Sanchez-Carvajal JM
AD  - Department of Anatomy and Comparative Pathology and Toxicology, International 
      Agrifood Campus of Excellence (ceiA3), Faculty of Veterinary Medicine, University 
      of Cordoba, Cordoba, Spain.
FAU - Guil-Luna, Silvia
AU  - Guil-Luna S
AD  - Maimonides Institute for Biomedical Research of Cordoba, IMIBIC, Cordoba, Spain.
FAU - Larenas-Munoz, Fernanda
AU  - Larenas-Munoz F
AD  - Department of Anatomy and Comparative Pathology and Toxicology, International 
      Agrifood Campus of Excellence (ceiA3), Faculty of Veterinary Medicine, University 
      of Cordoba, Cordoba, Spain.
FAU - Pallares, Francisco J
AU  - Pallares FJ
AD  - Department of Anatomy and Comparative Pathology and Toxicology, International 
      Agrifood Campus of Excellence (ceiA3), Faculty of Veterinary Medicine, University 
      of Cordoba, Cordoba, Spain.
FAU - Carrasco, Librado
AU  - Carrasco L
AD  - Department of Anatomy and Comparative Pathology and Toxicology, International 
      Agrifood Campus of Excellence (ceiA3), Faculty of Veterinary Medicine, University 
      of Cordoba, Cordoba, Spain.
FAU - Gomez-Laguna, Jaime
AU  - Gomez-Laguna J
AD  - Department of Anatomy and Comparative Pathology and Toxicology, International 
      Agrifood Campus of Excellence (ceiA3), Faculty of Veterinary Medicine, University 
      of Cordoba, Cordoba, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210511
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
SB  - IM
MH  - Animals
MH  - Porcine Reproductive and Respiratory Syndrome/*immunology/virology
MH  - Porcine respiratory and reproductive syndrome virus/*immunology/*pathogenicity
MH  - Swine
MH  - Thymus Gland/*immunology/*virology
MH  - Up-Regulation
MH  - Virulence
PMC - PMC8144631
OTO - NOTNLM
OT  - PRRSV
OT  - T-cell exhaustion
OT  - immune checkpoints
OT  - immunosuppression
OT  - thymus
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. The handling editor declared a past co-authorship with 
      several of the authors IR-T, FL-M, FP, LC, JG-L, IR-G, JS-C.
EDAT- 2021/05/29 06:00
MHDA- 2021/10/21 06:00
PMCR- 2021/01/01
CRDT- 2021/05/28 07:24
PHST- 2021/02/24 00:00 [received]
PHST- 2021/04/15 00:00 [accepted]
PHST- 2021/05/28 07:24 [entrez]
PHST- 2021/05/29 06:00 [pubmed]
PHST- 2021/10/21 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.671743 [doi]
PST - epublish
SO  - Front Immunol. 2021 May 11;12:671743. doi: 10.3389/fimmu.2021.671743. eCollection 
      2021.