Porcine reproductive and respiratory syndrome virus (PRRSV) predisposes pigs to secondary bacterial infection caused by Haemophilus parasuis. The aim of the present study was to analyse the immune response of monocyte-derived macrophages (MDMs), serving as a model of macrophages accumulating at the site of inflammation. The second part of the study was focused on the role of IFNα in the production of inflammatory cytokines in co-infected MDMs. Concurrent infection with PRRSV and H. parasuis decreased gene expression of pro-inflammatory cytokines (IL-1β, IL-8) in MDMs in comparison with MDMs infected with PRRSV or H. parasuis alone. Our data showed that MDMs express IFNα after PRRSV infection. Thereafter, we exposed cells to the experimental addition of IFNα and a subsequent infection with H. parasuis, and detected a decreased expression/production of pro-inflammatory cytokines. Thus, we assume that IFNα, produced after PRRSV infection, could affect the immune response of monocyte-derived macrophages. Down-regulation of pro-inflammatory cytokine expression in inflammatory macrophages may allow the development of secondary bacterial infections in pigs.
- MeSH
- bronchoalveolární laváž MeSH
- cytokiny genetika imunologie MeSH
- Haemophilus parasuis imunologie patogenita MeSH
- hemofilové infekce mikrobiologie veterinární MeSH
- interferon alfa imunologie farmakologie MeSH
- makrofágy účinky léků imunologie mikrobiologie virologie MeSH
- nemoci prasat mikrobiologie virologie MeSH
- prasata MeSH
- reprodukční a respirační syndrom prasat virologie MeSH
- viabilita buněk MeSH
- virus reprodukčního a respiračního syndromu prasat imunologie patogenita MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Porcine cytomegalovirus (PCMV) causes lifelong latent infections in swine. The pathogen is occasionally associated with inclusion body rhinitis and pneumonia in piglets, reproductive disorders in pregnant sows and respiratory disease complex in older pigs. Immunosuppressive potential of PCMV infection is discussed. Macrophages were recognised as one of target cell types where propagation of virus occurs. The aim of present study was to set up model PCMV infection of monocyte derived macrophages (MDMs) in vitro for PCMV immunobiology research. Obtained results showed that PCMV is able to infect and propagate in MDMs. Possible immunosuppressive effect of PCMV on infected macrophages was evaluated by measurement of immune relevant gene expression in MDMs. Infection decreased expression of IL-8 and TNF-α (pro-inflammatory cytokines) and increased expression of IL-10 (anti-inflammatory cytokine) on mRNA transcription level. Obtained data support hypothesis that higher sensitivity of animals to coinfection with other swine pathogens and its more severe clinical manifestations could potentially be the consequence of PCMV infection.
- MeSH
- cytokiny imunologie MeSH
- cytomegalovirové infekce imunologie veterinární MeSH
- Cytomegalovirus fyziologie MeSH
- exprese genu imunologie MeSH
- interleukin-10 imunologie MeSH
- interleukin-8 imunologie MeSH
- makrofágy imunologie virologie MeSH
- nemoci prasat imunologie virologie MeSH
- prasata MeSH
- přirozená imunita MeSH
- TNF-alfa imunologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant and economically important infectious diseases affecting swine worldwide and can predispose pigs to secondary bacterial infections caused by, e.g. Haemophilus parasuis. The aim of the presented study was to compare susceptibility of two different types of macrophages which could be in contact with both pathogens during infection with PRRS virus (PRRSV) and in co-infection with H. parasuis. Alveolar macrophages (PAMs) as resident cells provide one of the first lines of defence against microbes invading lung tissue. On the other hand, monocyte derived macrophages (MDMs) represent inflammatory cells accumulating at the site of inflammation. While PAMs were relatively resistant to cytopathogenic effect caused by PRRSV, MDMs were much more sensitive to PRRSV infection. MDMs infected with PRRSV increased expression of pro-apoptotic Bad, Bax and p53 mRNA. Increased mortality of MDMs may be also related to a higher intensity of ROS production after infection with PRRSV. In addition, MDMs (but not PAMs) infected with H. parasuis alone formed multinucleated giant cells (MGC); these cells were not observed in MDMs infected with both pathogens. Higher sensitivity of MDMs to PRRSV infection, which is associated with limited MDMs survival and restriction of MGC formation, could contribute to the development of multifactorial respiratory disease of swine.
- MeSH
- Haemophilus parasuis * MeSH
- hemofilové infekce komplikace patologie veterinární virologie MeSH
- koinfekce metabolismus patologie veterinární MeSH
- makrofágy metabolismus patologie virologie MeSH
- obrovské buňky metabolismus patologie virologie MeSH
- prasata MeSH
- pyrimidiny MeSH
- reaktivní formy kyslíku metabolismus MeSH
- reprodukční a respirační syndrom prasat metabolismus patologie virologie MeSH
- sulfonamidy MeSH
- virus reprodukčního a respiračního syndromu prasat * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
UNLABELLED: The HIV-1 envelope protein (Env) is heavily glycosylated, with approximately 50% of the Env molecular mass being contributed by N-glycans. HIV-1 Env N-glycans shield the protein backbone and have been shown to play key roles in determining Env structure, surface exposure, and, consequently, antigenicity, infectivity, antibody neutralization, and carbohydrate and receptor binding. Studies of HIV-1 glycosylation have focused mainly on the position of glycosylation, rather than the types of glycans. Also, the role of Env glycan moieties on HIV-1 transmission has not been systematically defined. Using viruses with modified Env glycan content and heterogeneity, we examined the effects of Env glycan moieties on the major events of HIV-1 transmission. Compared to viruses with less oligomannose and more complex Env glycans, viruses with more oligomannose and less complex glycans more efficiently (i) transcytosed across an epithelial cell monolayer, (ii) attached to monocyte-derived macrophages (MDMs), (iii) bound monocyte-derived dendritic cells (MoDCs), and (iv) trans-infected primary lymphocytes via MoDCs. However, viruses with more oligomannose and less complex glycans displayed impaired infectivity in TZMbl cells, MDMs, primary lymphocytes, and fresh human intestinal tissue. Thus, N-linked Env glycans display discordant effects on the major events of HIV-1 transmission, with mature oligosaccharide structures on Env playing a crucial role in HIV-1 infection. Env glycosylation should be taken into consideration in the development of vaccine strategies to interdict HIV-1 transmission. IMPORTANCE: HIV-1 Env N-glycans shield the protein backbone and play key roles in determining Env structure and surface exposure, thereby impacting Env antigenicity, infectivity, antibody neutralization, and carbohydrate and receptor binding. Studies of HIV-1 glycosylation have focused mainly on the position of glycosylation, rather than the types of glycans. In the study described in this report, we investigated systematically the role of Env glycan moieties on HIV-1 transmission. We show that N-linked Env glycans display discordant effects on the major events of HIV-1 transmission. These data indicate that Env glycan moieties impact HIV-1 transmission and that modulation of Env glycan moieties offers a potential strategy for the development of therapeutic or prophylactic vaccines against HIV-1.
- MeSH
- dendritické buňky virologie MeSH
- epitelové buňky virologie MeSH
- genové produkty env - virus lidské imunodeficience chemie metabolismus MeSH
- HIV-1 fyziologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- lymfocyty virologie MeSH
- makrofágy virologie MeSH
- polysacharidy analýza metabolismus MeSH
- přichycení viru * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- MeSH
- B-lymfocyty MeSH
- chronická nemoc MeSH
- cykliny genetika MeSH
- financování organizované MeSH
- Gammaherpesvirinae fyziologie genetika MeSH
- genom virový MeSH
- geny bcl-2 MeSH
- herpetické infekce virologie MeSH
- infekce onkogenními viry virologie MeSH
- latence viru MeSH
- lymfoproliferativní nemoci virologie MeSH
- makrofágy virologie MeSH
- modely nemocí na zvířatech MeSH
- proteiny bezprostředně časné fyziologie MeSH
- trans-aktivátory MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH