INTRODUCTION: Porcine reproductive and respiratory syndrome virus (PRRSV) emerged about 30 years ago and continues to cause major economic losses in the pork industry. The lack of effective modified live vaccines (MLV) allows the pandemic to continue. BACKGROUND AND OBJECTIVE: We have previously shown that wild strains of PRRSV affect the nascent T cell repertoire in the thymus, deplete T cell clones recognizing viral epitopes essential for neutralization, while triggering a chronic, robust, but ineffective antibody response. Therefore, we hypothesized that the current MLV are inappropriate because they cause similar damage and fail to prevent viral-induced dysregulation of adaptive immunity. METHODS: We tested three MLV strains to demonstrate that all have a comparable negative effect on thymocytes in vitro. Further in vivo studies compared the development of T cells in the thymus, peripheral lymphocytes, and antibody production in young piglets. These three MLV strains were used in a mixture to determine whether at least some of them behave similarly to the wild virus type 1 or type 2. RESULTS: Both the wild and MLV strains cause the same immune dysregulations. These include depletion of T-cell precursors, alteration of the TCR repertoire, necrobiosis at corticomedullary junctions, low body weight gain, decreased thymic cellularity, lack of virus-neutralizing antibodies, and production of non-neutralizing anti-PRRSV antibodies of different isotypes. DISCUSSION AND CONCLUSION: The results may explain why the use of current MLV in young animals may be ineffective and why their use may be potentially dangerous. Therefore, alternative vaccines, such as subunit or mRNA vaccines or improved MLV, are needed to control the PRRSV pandemic.
- MeSH
- atenuované vakcíny MeSH
- imunitní systém MeSH
- prasata MeSH
- protilátky virové MeSH
- reprodukční a respirační syndrom prasat * prevence a kontrola MeSH
- virus reprodukčního a respiračního syndromu prasat * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Interleukin-17A (IL-17) is a pro-inflammatory cytokine involved in the immune response to many pathogens playing also a role in certain chronic and autoimmune diseases. The presented study focused on the early postnatal development of IL-17 producing cells in swine. In agreement with previous studies, αβ T-helper (CD3+CD4+) and γδ T (CD3+TCRγδ+) cells were found to be the major producers of IL-17. In newborn conventional piglets, αβ T-helper cells positive for IL-17 were almost undetectable, but their frequency increased markedly with age in all issues examined, i.e., blood, spleen, and mesenteric lymph nodes (MLN). Additional analyses of CD8 and CD27 expression showed that the main αβ T-helper producers of IL-17 has CD8+CD27- phenotype in all tissues. IL-17 positive CD8+CD27+ αβ T-helper subpopulation was found only in blood and spleen. The production of IL17 in CD8-CD27+ αβ T-helper cells was always minor. In contrast, γδ T cells positive for IL-17 did not show a similar age-dependent increase in blood and spleen, whereas they increased in MLN. Because of the age-dependent increase in conventional animals, we included a comparison with germ-free piglets to show that the increase in IL-17 positive cells was clearly depended on the presence of the microbiota as the production in germ-free animals was negligible without any age-dependent increase.
The currently observed high prevalence of allergic diseases has been associated with changes in microbial exposure in industrialized countries. Defined bacterial components represent a new strategy for modulating the allergic immune response. We show that intranasal administration of exopolysaccharide (EPS) isolated from Lacticaseibacillus (L.) rhamnosus LOCK900 induces TGF-β1, IgA, and regulatory FoxP3+ T-cells in the lungs of naïve mice. Using the ovalbumin mouse model, we demonstrate that intranasal administration of EPS downregulates the development of allergic airway inflammation and the Th2 cytokine response in sensitized individuals. At the same time, EPS treatment of sensitized mice, similar to EPS-induced responses in naïve mice, significantly increased the level of total, OVA-specific, and also bacteria-specific IgA in bronchoalveolar lavage and the number of IgA-producing B-cells in the lung tissue of these mice. Thus, EPS derived from L. rhamnosus LOCK900 can be considered a safe candidate for preventing the development of allergic symptoms in the lungs of sensitized individuals upon exposure to an allergen.
- MeSH
- alergie * MeSH
- bronchoalveolární lavážní tekutina MeSH
- imunoglobulin A MeSH
- Lacticaseibacillus rhamnosus * MeSH
- Lacticaseibacillus MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- ovalbumin MeSH
- plíce MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The intestinal microbiota is known to influence postnatal growth. We previously found that a strain of Lactiplantibacillus plantarum (strain LpWJL) buffers the adverse effects of chronic undernutrition on the growth of juvenile germ-free mice. Here, we report that LpWJL sustains the postnatal growth of malnourished conventional animals and supports both insulin-like growth factor-1 (IGF-1) and insulin production and activity. We have identified cell walls isolated from LpWJL, as well as muramyl dipeptide and mifamurtide, as sufficient cues to stimulate animal growth despite undernutrition. Further, we found that NOD2 is necessary in intestinal epithelial cells for LpWJL-mediated IGF-1 production and for postnatal growth promotion in malnourished conventional animals. These findings indicate that, coupled with renutrition, bacteria cell walls or purified NOD2 ligands have the potential to alleviate stunting.
- MeSH
- acetylmuramyl-alanyl-isoglutamin farmakologie terapeutické užití MeSH
- buněčná stěna chemie MeSH
- epitelové buňky mikrobiologie fyziologie MeSH
- gnotobiologické modely MeSH
- insulinu podobný růstový faktor I metabolismus MeSH
- inzulin metabolismus MeSH
- Lactobacillaceae * fyziologie MeSH
- myši MeSH
- podvýživa * patofyziologie terapie MeSH
- poruchy růstu patofyziologie terapie MeSH
- růst * účinky léků fyziologie MeSH
- signální adaptorový protein Nod2 * metabolismus MeSH
- střeva * mikrobiologie fyziologie MeSH
- střevní mikroflóra * fyziologie MeSH
- střevní sliznice mikrobiologie fyziologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Studies in humans and mice indicate the critical role of the surrogate light chain in the selection of the productive immunoglobulin repertoire during B cell development. However, subsequent studies using mutant mice have also demonstrated that alternative pathways are allowed. Our recent investigation has shown that some species, such as pig, physiologically use preferential rearrangement of authentic light chains, and become independent of surrogate light chains. Here we summarize the findings from swine and compare them with results in other species. In both groups, allelic and isotypic exclusions remain intact, so the different processes do not alter the paradigm of B-cell monospecificity. Both groups also retained some other essential processes, such as segregated and sequential rearrangement of heavy and light chain loci, preferential rearrangement of light chain kappa before lambda, and functional κ-deleting element recombination. On the other hand, the respective order of heavy and light chains rearrangement may vary, and rearrangement of the light chain kappa and lambda on different chromosomes may occur independently. Studies have also confirmed that the surrogate light chain is not required for the selection of the productive repertoire of heavy chains and can be substituted by authentic light chains. These findings are important for understanding evolutional approaches, redundancy and efficiency of B-cell generation, dependencies on other regulatory factors, and strategies for constructing therapeutic antibodies in unrelated species. The results may also be important for explaining interspecies differences in the proportional use of light chains and for the understanding of divergences in rearrangement processes. Therefore, the division into two groups may not be definitive and there may be more groups of intermediate species.
- MeSH
- alely MeSH
- B-lymfocyty MeSH
- geny pro imunoglobuliny * MeSH
- imunoglobuliny - kappa-řetězce * genetika MeSH
- myši MeSH
- náhradní lehké řetězce imunoglobulinů genetika MeSH
- prasata MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Publikační typ
- abstrakt z konference MeSH
Mucosal surfaces are colonized by highly diverse commensal microbiota. Coating with secretory IgA (SIgA) promotes the survival of commensal bacteria while it inhibits the invasion by pathogens. Bacterial coating could be mediated by antigen-specific SIgA recognition, polyreactivity, and/or by the SIgA-associated glycans. In contrast to many in vitro studies, only a few reported the effect of SIgA glycans in vivo. Here, we used a germ-free antibody-free newborn piglets model to compare the protective effect of SIgA, SIgA with enzymatically removed N-glycans, Fab, and Fc containing the secretory component (Fc-SC) during oral necrotoxigenic E. coli O55 challenge. SIgA, Fab, and Fc-SC were protective, whereas removal of N-glycans from SIgA reduced SIgA-mediated protection as demonstrated by piglets' intestinal histology, clinical status, and survival. In vitro analyses indicated that deglycosylation of SIgA did not reduce agglutination of E. coli O55. These findings highlight the role of SIgA-associated N-glycans in protection. Further structural studies of SIgA-associated glycans would lead to the identification of those involved in the species-specific inhibition of attachment to corresponding epithelial cells.
- MeSH
- aglutinace MeSH
- Escherichia coli fyziologie MeSH
- glykosylace MeSH
- gnotobiologické modely MeSH
- imunoglobulin A sekreční metabolismus MeSH
- imunoglobuliny - Fab fragmenty metabolismus MeSH
- infekce vyvolané Escherichia coli imunologie MeSH
- jednořetězcové protilátky metabolismus MeSH
- novorozená zvířata MeSH
- odolnost vůči nemocem MeSH
- polysacharidy metabolismus MeSH
- prasata MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Developmental pathways for B cell lymphogenesis are sufficiently known only in mice and humans. However, both of these species rearrange immunoglobulin heavy chains (IgH) before light chains (IgL) while IgL precedes IgH rearrangement in swine. We demonstrate here that this reversed order of rearrangements have some concealed consequences: (1) we confirmed that although IgLκ rearrangement is initial, most IgLλ+ B cells are generated earlier and before IgH rearrangements, while most IgLκ+ B cells later and after IgH rearrangements, (2) the second IgLκ rearrangement can occur after IgLλ rearrangement, (3) early formed B cells bear only single in-frame IgH rearrangements, (4) many IgLκ+ B cells carry IgLλ rearrangements that can be productive and occurring on both alleles in one cell, and (5) although VpreB and λ5 genes are present in swine, they are preferentially expressed in non-B cells. In summary, our findings reveal that swine use an alternative B cell developmental pathway as compared to mice and humans.
- MeSH
- B-lymfocyty fyziologie MeSH
- buněčná diferenciace MeSH
- genová přestavba B-lymfocytů MeSH
- imunoglobuliny - kappa-řetězce genetika MeSH
- imunoglobuliny - lambda-řetězce genetika MeSH
- kultivované buňky MeSH
- lidé MeSH
- myši MeSH
- prasata imunologie MeSH
- receptory antigenů B-buněk genetika MeSH
- těžké řetězce imunoglobulinů genetika MeSH
- transkriptom MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Publikační typ
- abstrakt z konference MeSH
The aim of the present study was to evaluate the biodosimetric potential of peripheral blood lymphocytes, particularly of T-cell subsets (null and T helper) and natural killer cells (NK), upon exposure to gamma irradiation (60Co) in vivo. For this purpose, the change in relative numbers of NK cells and T-lymphocyte subsets, as well as in the H2AX phosphorylation rate, were evaluated as potential early markers of the lymphocytic response to irradiation in vivo. These experiments were performed on a Large White Pig model. As a result, significant but not dose-dependent changes in the proportion of lymphocyte subpopulations (NK cells, null and T helper cells) were found after exposure to ionising radiation in vivo. On the other hand, circulating NK cells showed relatively higher radioresistance capacity when compared to the T-lymphocyte subsets; however, gamma-H2AX expression showed no significant difference between the evaluated lymphocyte subsets.
- MeSH
- buňky NK účinky záření MeSH
- fenotyp MeSH
- fosforylace MeSH
- histony metabolismus MeSH
- imunofenotypizace MeSH
- ionizující záření MeSH
- lymfocyty cytologie MeSH
- poškození DNA MeSH
- prasata MeSH
- radioizotopy kobaltu farmakologie MeSH
- radiometrie metody MeSH
- T-lymfocyty - podskupiny účinky záření MeSH
- záření gama MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
