Activation of regulated cell death in the lung of piglets infected with virulent PRRSV-1 Lena strain occurs earlier and mediated by cleaved Caspase-8
Visualitza/Obre
Autor/a
Sánchez‑Carvajal, Jose María
Ruedas‑Torres, Inés
Carrasco, Librado
Pallarés, Francisco José
Mateu, Enric
Rodríguez‑Gómez, Irene Magdalena
Gómez‑Laguna, Jaime
Data de publicació
2021-01-22ISSN
0928-4249
Resum
PRRSV-1 virulent strains cause high fever, marked respiratory disease and severe lesions in lung and lymphoid organs. Regulated cell death (RCD), such as apoptosis, necroptosis and pyroptosis, is triggered by the host to interrupt viral replication eliminating infected cells, however, although it seems to play a central role in the immunopathogenesis of PRRSV, there are significant gaps regarding their sequence and activation upon PRRSV-infection. The present study evaluated RCD events by means of caspases expression in the lung of PRRSV-1-infected pigs and their impact on pulmonary macrophage subpopulations and lung lesion. Conventional piglets were intranasally inoculated with the virulent subtype 3 Lena strain or the low virulent subtype 1 3249 strain and euthanised at 1, 3, 6, 8 and 13 dpi. Lena-infected piglets showed severe and early lung damage with a high frequency of PRRSV-N-protein+ cells, depletion of CD163+ cells and high viral load in the lung. The number of TUNEL+ cells was significantly higher than cCasp3+ cells in Lena-infected piglets during the first week post-infection. cCasp8 and to a lesser extent cCasp9 were activated by both PRRSV-1 strains after one week post-infection together with a replenishment of both CD163+ and Arg-1+ pulmonary macrophages. These results highlight the induction of other forms of RCD beyond apoptosis, such as, necroptosis and pyroptosis during the first week post-infection followed by the activation of, mainly, extrinsic apoptosis during the second week post-infection. The recovery of CD163+ macrophages at the end of the study represents an attempt to restore pulmonary macrophage subpopulations lost during the early stages of the infection but also a macrophage polarisation into M2 macrophages.
Tipus de document
Article
Versió del document
Versió publicada
Llengua
English
Matèries (CDU)
619 - Veterinària
Pàgines
14
Publicat per
BMC
Publicat a
Veterinary Research
Citació
Sánchez-Carvajal, Jose María, Inés Ruedas-Torres, Librado Carrasco, Francisco José Pallarés, Enric Mateu, Irene Magdalena Rodríguez-Gómez, and Jaime Gómez-Laguna. 2021. "Activation Of Regulated Cell Death In The Lung Of Piglets Infected With Virulent PRRSV-1 Lena Strain Occurs Earlier And Mediated By Cleaved Caspase-8". Veterinary Research 52 (1). doi:10.1186/s13567-020-00882-x.
Número de l'acord de la subvenció
MINECO/Programa Estatal de I+D+I orientada a los retos de la sociedad/AGL2016-76111-R/ES/Caracterización del transcriptoma del macrófago alveolar porcino en las fases tempranas de la infección in vivo con cepas del virus del PRRS-1 de distinta virulencia/
MINECO/Programa Estatal de promoción del talento y su empleabilidad en I+D+I/RYC-2014-16735/ES/ /
MICIU/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I/PID2019-109718GB-100/ES/EVALUACION DE LOS PUNTOS DE CONTROL INMUNITARIO DURANTE LA INFECCION AGUDA Y CRONICA CON EL VIRUS DEL SINDROME REPRODUCTIVO Y RESPIRATORIO PORCINO/
Programa
Sanitat Animal
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