Morphological and Immunohistochemical Changes in Splenic Macrophages of Pigs Infected with Classical Swine Fever

Ruíz-Villamor, E.; Bautista, M.J.; Sánchez, Carmen; Sánchez-Cordón, P.J.; Salguero, Francisco J.; Jover, A

doi:10.1053/jcpa.2001.0487

Cited by 33 publications

(34 citation statements)

References 25 publications

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“…Thus, apoptosis among T-cell subpopulations, although less marked than in B-cell areas, may involve an indirect mechanism mediated by pro-apoptotic cytokines released by macrophages, as reported in other pestivirus infections (Gó mez-Villamandos et al, 2001;Sánchez-Cordó n et al, 2002.…”

Section: Liebler-tenoriomentioning

confidence: 85%

“…On the other hand, monocytes/macrophages may be involved in lymphocyte destruction through indirect mechanisms linked to the biosynthetic activation of macrophages (Lambot et al, 1998), which is the principal cause of lymphocyte apoptosis in the course of other viral diseases caused by pestiviruses such as CSFV (Gó mez-Villamandos et al, 2001;Sánchez-Cordó n et al, 2002.…”

Section: Introductionmentioning

confidence: 99%

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Apoptosis in lymphoid tissues of calves inoculated with non-cytopathic bovine viral diarrhea virus genotype 1: activation of effector caspase-3 and role of macrophages

Pedrera

Gómez-Villamandos

Romero-Trevejo

et al. 2009

Journal of General Virology

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The mechanisms responsible for lymphocyte apoptosis in bovine viral diarrhoea have not yet been clarified. Previous work suggests that bovine viral diarrhea virus (BVDV) is only directly responsible for the destruction of a small number of lymphocytes. The aim of this study was to clarify, in vivo, the role of macrophages in lymphocyte destruction through indirect mechanisms linked to the biosynthetic activation of these immunocompetent cells on ileal Peyer's patches, as well as the distribution and quantification of apoptosis. Eight colostrum-deprived calves were inoculated intranasally with a non-cytopathic strain of BVDV genotype 1 and killed in batches of two at 3, 6, 9 and 14 days post-inoculation (p.i.). The progressive depletion of Peyer's patches was found to be due to massive lymphocyte apoptosis, with an increase in cleaved caspase-3 and TUNEL-positive cells. Lymphoid depletion was accompanied, from 3 days p.i., by a significant rise in macrophage numbers both in lymphoid follicles and in interfollicular areas. Some macrophages showed signs of viral infection, together with subcellular changes indicative of phagocyte activation and, in some cases, of secretory activity. However, the number of macrophages that showed positive immunostaining for tumour necrosis factor-a and interleukin-1a, cytokines with a proven ability to induce apoptosis, remained low throughout the experiment in lymphoid follicles, where most apoptotic cells were found. These results thus appear to rule out a major involvement of macrophages and macrophage-secreted chemical mediators in the apoptosis of follicular B lymphocytes during BVDV infection. INTRODUCTIONApoptosis is a form of cell death recognized as an essential mechanism in morphogenesis and homeostasis of organs and tissues. The main morphological changes during apoptosis (cellular shrinkage, membrane blebbing, chromatin condensation at the nuclear periphery and nuclear fragmentation into apoptotic bodies) are the final result of a complex biochemical cascade of events (Huppertz et al., 1999;Rathmell & Thompson, 2002). The apoptosis cascade includes an initiation stage with induction of the cascade by external and internal stimuli, an execution stage with activation of effector proteases called caspases (cysteine-containing aspartic acid-specific proteases) and the apoptotic death stage including nuclear and cellular collapse (Huppertz et al., 1999;Hengartner, 2000). In vitro studies have elucidated two regulatory apoptosis pathways (intrinsic and extrinsic). Both pathways induce apoptosis via activation of the effector caspase-3, which, once activated, irreversibly executes cell death, so that activation of caspase-3 can be considered a hallmark of apoptosis (Stennicke et al., 1998;Huppertz et al., 1999).Apoptosis may also be involved in the immunopathogenesis of some viral diseases. There are several potential mechanisms by which viruses activate the apoptotic pathway. Some viruses may do so through the direct action of a specific viral protein (Noteborn et al., 1994;Zh...

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Section: Liebler-tenoriomentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Apoptosis in lymphoid tissues of calves inoculated with non-cytopathic bovine viral diarrhea virus genotype 1: activation of effector caspase-3 and role of macrophages

Pedrera

Gómez-Villamandos

Romero-Trevejo

et al. 2009

Journal of General Virology

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“…Further investigations would be necessary to ascertain that the viral immunogenic protein was processed in cDC and pDC, and/or to know if CSFV replicated in these cells. Uptake of viral antigen by APC is also supported by the recruitment of CD172a + and IFN-α + cells in both tonsil and spleen T cell areas and by the intriguing disappearance of [19,38,39].…”

Section: Discussionmentioning

confidence: 98%

Classical swine fever virus induces activation of plasmacytoid and conventional dendritic cells in tonsil, blood, and spleen of infected pigs

et al. 2007

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-Classical swine fever virus (CSFV) compromises the host immune system, causing indirect leucopoenia and disruption of in vitro T cell stimulation capacity. In order to explore the potential role of dendritic cells (DC) in such phenomena, the activation of conventional DC (cDC) and plasmacytoid DC (pDC) in blood and secondary lymphoid organs of infected pigs was investigated in the early time course post-inoculation (pi), together with viral components dissemination and cytokine production in serum. Whereas CD11R1 + CD172a + cDC frequencies were markedly reduced in blood and spleen, analysis of CD4 + CD172a + pDC numbers revealed a rapid turn-over of this DC subset in tissues pi. Both subsets matured and were activated after infection, as demonstrated by down-regulation of CD1a, up-regulation of the co-stimulation molecule CD80/86 and expression of cytokines. cDC essentially expressed tumor necrosis factor alpha (TNF-α) and interleukin (IL)-10, whereas pDC produced alpha interferon (IFN-α) and IL-12. IFN-α and TNF-α productions revealed an enhancement of innate anti-viral immune responses. Detection of antigen activated B lymphocytes in tonsil T-cell areas at 72 h pi, subsequently to the transient translocation of the viral E2 protein within germinal centres at 48 h pi, indicates the initiation of humoral response. This response was also evidenced by an important IL-10 production in serum one week pi. IL-12 expression in organs, as well as transient detection of IL-18 and IFN-γ in serum, reflected the initiation of cellular immune responses. However, the uncommonly high levels of TNF-α and IFN-α produced by DC and measured in serum early post-infection, together with IL-10 expression in spleen, could play a role in the disruption of immune system cells, either inducing apoptosis or impairing DC functionalities themselves.antigen presenting cells / secondary lymphoid organs / interferon / E2 antigen / pestivirus

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“…8 Attention is also drawn to the procoagulant activity of both TNF-␣ and IL-1 and, to a lesser extent, IL-6, 16,46 as well as to the involvement of TNF-␣, together with tissue damage, in the activation of the extrinsic coagulation pathway. 52 Numerous studies have shown that the m-Mø is the prime target cell of classical swine fever (CSF) or hog cholera virus, 21,41,42,47 although lymphocyte infection is also reported in later stages of the disease. 21,47,49 The pathogenic mechanisms involved in the thrombocytopenia and lymphoid depletion observed in CSF remain unclear.…”

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confidence: 99%

“…19,47 Recent research suggests that changes in the function of m-Møs, prompted by infection, alter the secretory properties of these cells; this alteration, coupled with their mobility, may be a decisive factor in the pathogenesis of the disease. 21,41,42 CSF thus affords a useful animal model for biomedical research into the pathogenesis of human virus infections prompting immunosuppression and hemorrhage. Moreover, given its anatomic and physiologic characteristics, the pig is seen as a likely source of organs for xenotransplantation; therefore, more detailed knowledge is required regarding its immune system and the potential consequences of the transmission of pathogens to humans treated with living pig tissues.…”

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confidence: 99%

Lymphocyte Apoptosis and Thrombocytopenia in Spleen during Classical Swine Fever: Role of Macrophages and Cytokines

et al. 2005

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Abstract. Thirty-two Large White ϫ Landrace pigs, 4 months old, were inoculated with the classical swine fever (CSF) or hog cholera virus strain ''Alfort'' in order to identify the mechanism responsible for the lymphopenia and thrombocytopenia observed in the spleen during the experimental induction of disease, by immunohistochemical and ultrastructural techniques. Results showed a progressive depletion of splenic lymphoid structures and evidence of platelet aggregation processes. Lymphoid depletion was due to lymphocyte apoptosis, which could not be ascribed to the direct action of the virus on these cells; direct virus action could play only a secondary role in the death of these cells. Absence of severe tissue and endothelial damage, together with moderate procoagulant cytokine levels in the serum, suggest that these pathologies can be ruled out as the cause of platelet aggregation and thrombocytopenia in CSF. Monocyte/macrophages were the main target cells for the CSF virus, and they exhibited phagocytic and secretory activation leading to the synthesis and release of tumor necrosis factor ␣, which proved to be the chief mediator, followed by IL-6, IL-1␣, and C1q complement component. In view of their characteristics, TNF-␣ and, to a lesser extent, IL-1␣ and IL-6 appear to be the major cytokines involved in the pathogenesis of lymphocytopenia and thrombocytopenia; a clear spatial and temporal relationship was observed between these two phenomena.

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Morphological and Immunohistochemical Changes in Splenic Macrophages of Pigs Infected with Classical Swine Fever

Cited by 33 publications

References 25 publications

Apoptosis in lymphoid tissues of calves inoculated with non-cytopathic bovine viral diarrhea virus genotype 1: activation of effector caspase-3 and role of macrophages

Apoptosis in lymphoid tissues of calves inoculated with non-cytopathic bovine viral diarrhea virus genotype 1: activation of effector caspase-3 and role of macrophages

Classical swine fever virus induces activation of plasmacytoid and conventional dendritic cells in tonsil, blood, and spleen of infected pigs

Lymphocyte Apoptosis and Thrombocytopenia in Spleen during Classical Swine Fever: Role of Macrophages and Cytokines

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