Thymic depletion of lymphocytes is associated with the virulence of PRRSV-1 strains

Amarilla, Shyrley Paola; Gómez-Laguna, J.; Carrasco, L.; Rodríguez-Gómez, I.M.; Ocerín, José María Caridad y; Graham, Simon P.; Frossard, Jean-Pierre; Steinbach, Falko; Salguero, Francisco J.

doi:10.1016/j.vetmic.2016.04.005

Cited by 18 publications

(16 citation statements)

References 36 publications

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“…Therefore, PRRSV, as well as many other viruses, have developed strategies to obstruct or delay apoptosis in order to obtain a window of time in which viral replication, self-assembly and release can take place [26,34,35,49]. It has been showed that PRRSV-induced apoptosis is reliant on virulencestrain since PRRSV-1 virulent strains cause apoptosis and necrosis with a higher severity in lymphoid organs than low virulent strains [9][10][11]. However, the mechanisms involved in RCD phenomena used by virulent strains in the lung of PRRSV-1 infected pigs have not been elucidated yet.…”

Section: Discussionmentioning

confidence: 99%

“…Lung lesion can range from the typical interstitial pneumonia observed with low virulent strains to suppurative bronchopneumonia after infection with virulent strains, usually associated with secondary bacterial infection [3,5,7]. In this line, although apoptosis and necrosis have been well characterised in lymphoid organs of virulent PRRSV-1-infected animals [8][9][10][11], limited information is available regarding the onset of cell death phenomena in the lung.…”

Section: Introductionmentioning

confidence: 99%

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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

Sánchez‐Carvajal

Ruedas‐Torres

Carrasco

et al. 2021

Vet Res

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Sánchez‐Carvajal

Ruedas‐Torres

Carrasco

et al. 2021

Vet Res

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“…PRRSV does neither; infection does not lead to severe lymphoid depletion or ablation, and it does not interfere profoundly with lymphocyte differentiation or maturation. Leukocyte perturbations in lymphoid tissues are associated with PRRSV infection, suggesting that adaptive immunity might be weakened, though not destroyed [56,57,58,59,60,61]. …”

Section: Immunosuppressionmentioning

confidence: 99%

Mechanisms of Adaptive Immunity to Porcine Reproductive and Respiratory Syndrome Virus

Rahe

Murtaugh

2017

Viruses

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The adaptive immune response is necessary for the development of protective immunity against infectious diseases. Porcine reproductive and respiratory syndrome virus (PRRSV), a genetically heterogeneous and rapidly evolving RNA virus, is the most burdensome pathogen of swine health and wellbeing worldwide. Viral infection induces antigen-specific immunity that ultimately clears the infection. However, the resulting immune memory, induced by virulent or attenuated vaccine viruses, is inconsistently protective against diverse viral strains. The immunological mechanisms by which primary and memory protection are generated and used are not well understood. Here, we summarize current knowledge regarding cellular and humoral components of the adaptive immune response to PRRSV infection that mediate primary and memory immune protection against viruses.

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“…This correlated with a delayed antibody response and a decrease in helper cell-associated IL-4 (42). Thymus atrophy (Figures 4A,C) can explain PRRS-related lymphopenia (27, 28, 30, 42) and its severity is directly correlated with strain virulence (44, 46). Immunohistochemical studies indicate that thymocytes are undergoing apoptosis (Figure 4F) and flow cytometric studies show that DP thymocytes are depleted (Figures 5A,B).…”

Section: Background and Hypothesismentioning

confidence: 99%

Perturbation of Thymocyte Development Underlies the PRRS Pandemic: A Testable Hypothesis

et al. 2019

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Porcine reproductive and respiratory syndrome virus (PRRSV) causes immune dysregulation during the Critical Window of Immunological Development. We hypothesize that thymocyte development is altered by infected thymic antigen presenting cells (TAPCs) in the fetal/neonatal thymus that interact with double-positive thymocytes causing an acute deficiency of T cells that produces “holes” in the T cell repertoire allowing for poor recognition of PRRSV and other neonatal pathogens. The deficiency may be the result of random elimination of PRRSV-specific T cells or the generation of T cells that accept PRRSV epitopes as self-antigens. Loss of helper T cells for virus neutralizing (VN) epitopes can result in the failure of selection for B cells in lymph node germinal centers capable of producing high affinity VN antibodies. Generation of cytotoxic and regulatory T cells may also be impaired. Similar to infections with LDV, LCMV, MCMV, HIV-1 and trypanosomes, the host responds to the deficiency of pathogen-specific T cells and perhaps regulatory T cells, by “last ditch” polyclonal B cell activation. In colostrum-deprived PRRSV-infected isolator piglets, this results in hypergammaglobulinemia, which we believe to be a “red herring” that detracts attention from the thymic atrophy story, but leads to our second independent hypothesis. Since hypergammaglobulinemia has not been reported in PRRSV-infected conventionally-reared piglets, we hypothesize that this is due to the down-regulatory effect of passive maternal IgG and cytokines in porcine colostrum, especially TGFβ which stimulates development of regulatory T cells (Tregs).

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Thymic depletion of lymphocytes is associated with the virulence of PRRSV-1 strains

Cited by 18 publications

References 36 publications

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

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

Mechanisms of Adaptive Immunity to Porcine Reproductive and Respiratory Syndrome Virus

Perturbation of Thymocyte Development Underlies the PRRS Pandemic: A Testable Hypothesis

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