PRRSV-1 induced lung lesion is associated with an imbalance between costimulatory and coinhibitory immune checkpoints
Porcine reproductive and respiratory syndrome virus (PRRSV) induces a dysregulation on the innate and adaptive immune responses. T-cell activation requires a proper interaction and precise balance between costimulatory and coinhibitory molecules, commonly known as immune checkpoints. This study aims...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-01-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.1007523/full |
| _version_ | 1797955269997625344 |
|---|---|
| author | Inés Ruedas-Torres José María Sánchez-Carvajal Librado Carrasco Francisco José Pallarés Fernanda Larenas-Muñoz Irene Magdalena Rodríguez-Gómez Jaime Gómez-Laguna |
| author_facet | Inés Ruedas-Torres José María Sánchez-Carvajal Librado Carrasco Francisco José Pallarés Fernanda Larenas-Muñoz Irene Magdalena Rodríguez-Gómez Jaime Gómez-Laguna |
| author_sort | Inés Ruedas-Torres |
| collection | DOAJ |
| description | Porcine reproductive and respiratory syndrome virus (PRRSV) induces a dysregulation on the innate and adaptive immune responses. T-cell activation requires a proper interaction and precise balance between costimulatory and coinhibitory molecules, commonly known as immune checkpoints. This study aims to evaluate the expression of immune checkpoints in lung and tracheobronchial lymph node from piglets infected with two PRRSV-1 strains of different virulence during the early stage of infection. Seventy 4-week-old piglets were grouped into three experimental groups: (i) control, (ii) 3249-infected group (low virulent strain), and (iii) Lena-infected group (virulent strain) and were euthanized at 1, 3, 6, 8, and 13 days post-infection (dpi). Lung and tracheobronchial lymph node were collected to evaluate histopathological findings, PRRSV viral load and mRNA expression of costimulatory (CD28, CD226, TNFRSF9, SELL, ICOS, and CD40) and coinhibitory (CTLA4, TIGIT, PD1/PDL1, TIM3, LAG3, and IDO1) molecules through RT-qPCR. Our findings highlight a mild increase of costimulatory molecules together with an earlier and stronger up-regulation of coinhibitory molecules in both organs from PRRSV-1-infected animals, especially in the lung from virulent Lena-infected animals. The simultaneous expression of coinhibitory immune checkpoints could work in synergy to control and limit the inflammation-induced tissue damage. Further studies should be addressed to determine the role of these molecules in later stages of PRRSV infection. |
| first_indexed | 2024-04-10T23:30:24Z |
| format | Article |
| id | doaj.art-2db17642a3e54dd787fc18235d869a30 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-10T23:30:24Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-2db17642a3e54dd787fc18235d869a302023-01-12T06:26:42ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-01-011310.3389/fmicb.2022.10075231007523PRRSV-1 induced lung lesion is associated with an imbalance between costimulatory and coinhibitory immune checkpointsInés Ruedas-TorresJosé María Sánchez-CarvajalLibrado CarrascoFrancisco José PallarésFernanda Larenas-MuñozIrene Magdalena Rodríguez-GómezJaime Gómez-LagunaPorcine reproductive and respiratory syndrome virus (PRRSV) induces a dysregulation on the innate and adaptive immune responses. T-cell activation requires a proper interaction and precise balance between costimulatory and coinhibitory molecules, commonly known as immune checkpoints. This study aims to evaluate the expression of immune checkpoints in lung and tracheobronchial lymph node from piglets infected with two PRRSV-1 strains of different virulence during the early stage of infection. Seventy 4-week-old piglets were grouped into three experimental groups: (i) control, (ii) 3249-infected group (low virulent strain), and (iii) Lena-infected group (virulent strain) and were euthanized at 1, 3, 6, 8, and 13 days post-infection (dpi). Lung and tracheobronchial lymph node were collected to evaluate histopathological findings, PRRSV viral load and mRNA expression of costimulatory (CD28, CD226, TNFRSF9, SELL, ICOS, and CD40) and coinhibitory (CTLA4, TIGIT, PD1/PDL1, TIM3, LAG3, and IDO1) molecules through RT-qPCR. Our findings highlight a mild increase of costimulatory molecules together with an earlier and stronger up-regulation of coinhibitory molecules in both organs from PRRSV-1-infected animals, especially in the lung from virulent Lena-infected animals. The simultaneous expression of coinhibitory immune checkpoints could work in synergy to control and limit the inflammation-induced tissue damage. Further studies should be addressed to determine the role of these molecules in later stages of PRRSV infection.https://www.frontiersin.org/articles/10.3389/fmicb.2022.1007523/fullimmune checkpointsdysregulationlunglymph nodePRRSVvirulence |
| spellingShingle | Inés Ruedas-Torres José María Sánchez-Carvajal Librado Carrasco Francisco José Pallarés Fernanda Larenas-Muñoz Irene Magdalena Rodríguez-Gómez Jaime Gómez-Laguna PRRSV-1 induced lung lesion is associated with an imbalance between costimulatory and coinhibitory immune checkpoints Frontiers in Microbiology immune checkpoints dysregulation lung lymph node PRRSV virulence |
| title | PRRSV-1 induced lung lesion is associated with an imbalance between costimulatory and coinhibitory immune checkpoints |
| title_full | PRRSV-1 induced lung lesion is associated with an imbalance between costimulatory and coinhibitory immune checkpoints |
| title_fullStr | PRRSV-1 induced lung lesion is associated with an imbalance between costimulatory and coinhibitory immune checkpoints |
| title_full_unstemmed | PRRSV-1 induced lung lesion is associated with an imbalance between costimulatory and coinhibitory immune checkpoints |
| title_short | PRRSV-1 induced lung lesion is associated with an imbalance between costimulatory and coinhibitory immune checkpoints |
| title_sort | prrsv 1 induced lung lesion is associated with an imbalance between costimulatory and coinhibitory immune checkpoints |
| topic | immune checkpoints dysregulation lung lymph node PRRSV virulence |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.1007523/full |
| work_keys_str_mv | AT inesruedastorres prrsv1inducedlunglesionisassociatedwithanimbalancebetweencostimulatoryandcoinhibitoryimmunecheckpoints AT josemariasanchezcarvajal prrsv1inducedlunglesionisassociatedwithanimbalancebetweencostimulatoryandcoinhibitoryimmunecheckpoints AT libradocarrasco prrsv1inducedlunglesionisassociatedwithanimbalancebetweencostimulatoryandcoinhibitoryimmunecheckpoints AT franciscojosepallares prrsv1inducedlunglesionisassociatedwithanimbalancebetweencostimulatoryandcoinhibitoryimmunecheckpoints AT fernandalarenasmunoz prrsv1inducedlunglesionisassociatedwithanimbalancebetweencostimulatoryandcoinhibitoryimmunecheckpoints AT irenemagdalenarodriguezgomez prrsv1inducedlunglesionisassociatedwithanimbalancebetweencostimulatoryandcoinhibitoryimmunecheckpoints AT jaimegomezlaguna prrsv1inducedlunglesionisassociatedwithanimbalancebetweencostimulatoryandcoinhibitoryimmunecheckpoints |