Many highly effective vaccines have been produced against viruses whose virulent infection elicits strong and durable protective immunity. In these cases, characterization of immune effector ...mechanisms and identification of protective epitopes/immunogens has been informative for the development of successful vaccine programs. Diseases in which the immune system does not rapidly clear the acute infection and/or convalescent immunity does not provide highly effective protection against secondary challenge pose a major hurdle for clinicians and scientists. Porcine reproductive and respiratory syndrome virus (PRRSV) falls primarily into this category, though not entirely. PRRSV causes a prolonged infection, though the host eventually clears the virus. Neutralizing antibodies can provide passive protection when present prior to challenge, though infection can be controlled in the absence of detectable neutralizing antibodies. In addition, primed pigs (through natural exposure or vaccination with a modified-live vaccine) show some protection against secondary challenge. While peripheral PRRSV-specific T cell responses have been examined, their direct contribution to antibody-mediated immunity and viral clearance have not been fully elucidated. The innate immune response following PRRSV infection, particularly the antiviral type I interferon response, is meager, but when provided exogenously, IFN-α enhances PRRSV immunity and viral control. Overall, the quality of immunity induced by natural PRRSV infection is not ideal for informing vaccine development programs.
The epitopes necessary for protection may be identified through natural exposure or modified-live vaccines and subsequently applied to vaccine delivery platforms to accelerate induction of protective immunity following vaccination. Collectively, further work to identify protective B and T cell epitopes and mechanisms by which PRRSV eludes innate immunity will enhance our ability to develop more effective methods to control and eliminate PRRS disease.
Antimicrobial resistance (AMR) is a significant problem in health care, animal health, and food safety. To limit AMR, there is a need for alternatives to antibiotics to enhance disease resistance and ...support judicious antibiotic usage in animals and humans. Immunomodulation is a promising strategy to enhance disease resistance without antibiotics in food animals. One rapidly evolving field of immunomodulation is innate memory in which innate immune cells undergo epigenetic changes of chromatin remodeling and metabolic reprogramming upon a priming event that results in either enhanced or suppressed responsiveness to secondary stimuli (training or tolerance, respectively). Exposure to live agents such as bacille Calmette-Guerin (BCG) or microbe-derived products such as LPS or yeast cell wall ß-glucans can reprogram or "train" the innate immune system. Over the last decade, significant advancements increased our understanding of innate training in humans and rodent models, and strategies are being developed to specifically target or regulate innate memory. In veterinary species, the concept of enhancing the innate immune system is not new; however, there are few available studies which have purposefully investigated innate training as it has been defined in human literature. The development of targeted approaches to engage innate training in food animals, with the practical goal of enhancing the capacity to limit disease without the use of antibiotics, is an area which deserves attention. In this review, we provide an overview of innate immunomodulation and memory, and the mechanisms which regulate this long-term functional reprogramming in other animals (e.g., humans, rodents). We focus on studies describing innate training, or similar phenomenon (often referred to as heterologous or non-specific protection), in cattle, sheep, goats, swine, poultry, and fish species; and discuss the potential benefits and shortcomings of engaging innate training for enhancing disease resistance.
Pigs play an important role in influenza A virus (IAV) epidemiology because they support replication of human, avian, and swine origin viruses and act as an IAV reservoir for pigs and other species, ...including humans. Moreover, novel IAVs with human pandemic potential may be generated in pigs. To minimize the threat of IAVs to human and swine health, it is crucial to understand host defense mechanisms that restrict viral replication and pathology in pigs. In this article, we review IAV strains circulating in the North American swine population, as well as porcine innate and acquired immune responses to IAV, including recent advances achieved through immunological tools developed specifically for swine. Furthermore, we highlight unique aspects of the porcine pulmonary immune system, which warrant consideration when developing vaccines and therapeutics to limit IAV in swine or when using pigs to model human IAV infections.
Intraepithelial lymphocytes (IELs) include T cells and innate lymphoid cells that are important mediators of intestinal immunity and barrier defense, yet most knowledge of IELs is derived from the ...study of humans and rodent models. Pigs are an important global food source and promising biomedical model, yet relatively little is known about IELs in the porcine intestine, especially during formative ages of intestinal development. Due to the biological significance of IELs, global importance of pig health, and potential of early life events to influence IELs, we collate current knowledge of porcine IEL functional and phenotypic maturation in the context of the developing intestinal tract and outline areas where further research is needed. Based on available findings, we formulate probable implications of IELs on intestinal and overall health outcomes and highlight key findings in relation to human IELs to emphasize potential applicability of pigs as a biomedical model for intestinal IEL research. Review of current literature suggests the study of porcine intestinal IELs as an exciting research frontier with dual application for betterment of animal and human health.
Haemophilus parasuis is a Gram-negative bacterium that colonizes the upper respiratory tract of swine and is capable of causing a systemic infection, resulting in high morbidity and mortality. H. ...parasuis isolates display a wide range of virulence and virulence factors are largely unknown. Commercial bacterins are often used to vaccinate swine against H. parasuis, though strain variability and lack of cross-reactivity can make this an ineffective means of protection. Outer membrane vesicles (OMV) are spherical structures naturally released from the membrane of bacteria and OMV are often enriched in toxins, signaling molecules and other bacterial components. Examination of OMV structures has led to identification of virulence factors in a number of bacteria and they have been successfully used as subunit vaccines. We have isolated OMV from both virulent and avirulent strains of H. parasuis, have examined their protein content and assessed their ability to induce an immune response in the host. Vaccination with purified OMV derived from the virulent H. parasuis Nagasaki strain provided protection against challenge with a lethal dose of the bacteria.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Interactions between diet, the microbiota, and the host set the ecological conditions in the gut and have broad implications for health. Prebiotics are dietary compounds that may shift conditions ...toward health by promoting the growth of beneficial microbes that produce metabolites capable of modulating host cells. This study's objective was to assess how a dietary prebiotic could impact host tissues via modulation of the intestinal microbiota. Pigs fed a diet amended with 5% resistant potato starch (RPS) exhibited alterations associated with gut health relative to swine fed an unamended control diet (CON). RPS intake increased abundances of anaerobic
in feces and several tissues, as well as intestinal concentrations of butyrate. Functional gene amplicons suggested bacteria similar to
were stimulated by RPS intake. The CON treatment exhibited increased abundances of several genera of
(which utilize respiratory metabolisms) in several intestinal locations. RPS intake increased the abundance of regulatory T cells in the cecum, but not periphery, and cecal immune status alterations were indicative of enhanced mucosal defenses. A network analysis of host and microbial changes in the cecum revealed that regulatory T cells positively correlated with butyrate concentration, luminal IgA concentration, expression of IL-6 and DEF1B, and several mucosa-associated bacterial taxa. Thus, the administration of RPS modulated the microbiota and host immune status, altering markers of cecal barrier function and immunological tolerance, and suggesting a reduced niche for bacterial respiration.
Vaccine-induced disease enhancement has been described in connection with several viral vaccines in animal models and in humans. We investigated a swine model to evaluate mismatched influenza ...vaccine-associated enhanced respiratory disease (VAERD) after pH1N1 infection. Vaccinating pigs with whole inactivated H1N2 (human-like) virus vaccine (WIV-H1N2) resulted in enhanced pneumonia and disease after pH1N1 infection. WIV-H1N2 immune sera contained high titers of cross-reactive anti-pH1N1 hemagglutinin (HA) antibodies that bound exclusively to the HA2 domain but not to the HA1 globular head. No hemagglutination inhibition titers against pH1N1 (challenge virus) were measured. Epitope mapping using phage display library identified the immunodominant epitope recognized by WIV-H1N2 immune sera as amino acids 32 to 77 of pH1N1-HA2 domain, close to the fusion peptide. These cross-reactive anti-HA2 antibodies enhanced pH1N1 infection of Madin-Darby canine kidney cells by promoting virus membrane fusion activity. The enhanced fusion activity correlated with lung pathology in pigs. This study suggests a role for fusion-enhancing anti-HA2 antibodies in VAERD, in the absence of receptor-blocking virus-neutralizing antibodies. These findings should be considered during the evaluation of universal influenza vaccines designed to elicit HA2 stem-targeting antibodies.
Post-weaning diarrhea caused by enterotoxigenic
E. coli
(ETEC) causes significant economic losses for pig producers. This study was to test the hypotheses that an ETEC challenge disrupts intestinal ...microbial homeostasis and the inclusion of dietary soluble (10% sugar beet pulp) or insoluble fiber (15% corn distillers dried grains with solubles) with or without exogenous carbohydrases will protect or restore the gut microbial homeostasis in weaned pigs. Sixty crossbred piglets (6.9 ± 0.1 kg) were blocked by body weight and randomly assigned to one of six treatments (
n
= 10), including a non-challenged control (NC), ETEC F18-challenged positive control (PC), ETEC-challenged soluble fiber without (SF-) or with carbohydrases (SF+), and ETEC-challenged insoluble fiber without (IF-) or with carbohydrases (IF+). Pigs were housed individually and orally received either ETEC inoculum or PBS-sham inoculum on day 7 post-weaning. Intestinal contents were collected on day 14 or 15. The V4 region of the bacterial 16S rRNA was amplified and sequenced. High-quality reads (total 6,671,739) were selected and clustered into 3,330 OTUs. No differences were observed in α-diversity among treatments. The ileal microbiota in NC and PC had modest separation in the weighted PCoA plot; the microbial structures were slightly altered by SF+ and IF- compared with PC. The PC increased ileal
Escherichia-Shigella
(
P
< 0.01) and numerically decreased
Lactobacillus
compared to NC. Predicted functional pathways enriched in the ileal microbiota of PC pigs indicated enhanced activity of Gram-negative bacteria, in agreement with increased
Escherichia-Shigella
. The SF+ tended to decrease (
P
< 0.10) ileal
Escherichia-Shigella
compared to PC. Greater abundance of ileal
Streptococcus
,
Turicibacter
, and
Roseburia
and colonic
Prevotella
were observed in SF- and SF+ than PC (
P
< 0.05). Pigs fed IF + had greater
Lactobacillus
and
Roseburia
than PC pigs (
P
< 0.05). The ETEC challenge reduced total volatile fatty acid (VFA) compared with NC (
P
< 0.05). The SF+ tended to increase (
P
< 0.10) and SF- significantly increased (
P
< 0.05) colonic total VFA compared with PC. Collectively, ETEC challenge disrupted gut microbial homeostasis and impaired microbial fermentation capacity. Soluble fiber improved VFA production. Dietary fiber and carbohydrases altered microbiota composition to maintain or restore microbial homeostasis.
Pigs are a valuable human biomedical model and an important protein source supporting global food security. The transcriptomes of peripheral blood immune cells in pigs were defined at the bulk ...cell-type and single cell levels. First, eight cell types were isolated in bulk from peripheral blood mononuclear cells (PBMCs) by cell sorting, representing Myeloid, NK cells and specific populations of T and B-cells. Transcriptomes for each bulk population of cells were generated by RNA-seq with 10,974 expressed genes detected. Pairwise comparisons between cell types revealed specific expression, while enrichment analysis identified 1,885 to 3,591 significantly enriched genes across all 8 cell types. Gene Ontology analysis for the top 25% of significantly enriched genes (SEG) showed high enrichment of biological processes related to the nature of each cell type. Comparison of gene expression indicated highly significant correlations between pig cells and corresponding human PBMC bulk RNA-seq data available in Haemopedia. Second, higher resolution of distinct cell populations was obtained by single-cell RNA-sequencing (scRNA-seq) of PBMC. Seven PBMC samples were partitioned and sequenced that produced 28,810 single cell transcriptomes distributed across 36 clusters and classified into 13 general cell types including plasmacytoid dendritic cells (DC), conventional DCs, monocytes, B-cell, conventional CD4 and CD8 αβ T-cells, NK cells, and γδ T-cells. Signature gene sets from the human Haemopedia data were assessed for relative enrichment in genes expressed in pig cells and integration of pig scRNA-seq with a public human scRNA-seq dataset provided further validation for similarity between human and pig data. The sorted porcine bulk RNAseq dataset informed classification of scRNA-seq PBMC populations; specifically, an integration of the datasets showed that the pig bulk RNAseq data helped define the CD4CD8 double-positive T-cell populations in the scRNA-seq data. Overall, the data provides deep and well-validated transcriptomic data from sorted PBMC populations and the first single-cell transcriptomic data for porcine PBMCs. This resource will be invaluable for annotation of pig genes controlling immunogenetic traits as part of the porcine Functional Annotation of Animal Genomes (FAANG) project, as well as further study of, and development of new reagents for, porcine immunology.
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