Philip Griebel | University of Saskatchewan (original) (raw)
Papers by Philip Griebel
Veterinary Vaccines: Current Innovations and Future Trends, 2020
Journal of Dairy Science, 2020
Journal of Animal Science, 2019
Mycobacterium avium subsp. Paratuberculosis (MAP) is the causal agent of Johne’s disease (JD), a ... more Mycobacterium avium subsp. Paratuberculosis (MAP) is the causal agent of Johne’s disease (JD), a chronic intestinal disease affecting ruminants worldwide. This study investigated miRNA expression in jejunal intestine (JE) and jejunal lymph nodes (JELN), and the potential regulatory roles of miRNAs during JD progression. JE and JELN tissues were collected from 5 MAP positive (JD subclinical stage) Holstein cows and 5 MAP negative cows. Following miRNA sequencing, bioinformatic processing with a standard pipeline and functional analysis with ClueGo, 272 and 333 miRNAs were identified in JE and JELN, respectively. Compared with MAP negative cows, 13 and 71 miRNAs were differently expressed (DE) (P < 0.05) in MAP infected JE and JELN, respectively. The most up-regulated and down-regulated miRNAs were bta-miR-485 (fold change = 6.18) and bta-miR-451 (fold change = -6.81), and bta-miR-331-5p (fold change = 35.56) and bta-miR-2285bk (fold change = -61.25) in JE and JELN, respectively. I...
Human Vaccines & Immunotherapeutics, 2019
Veterinary Immunology and Immunopathology, 2009
Immunology, 1999
The majority of pathogens enter the body through mucosal surfaces and it is now evident that muco... more The majority of pathogens enter the body through mucosal surfaces and it is now evident that mucosal immunity can provide effective disease protection. However, the induction of mucosal immunity will require efficient targeting of mucosal vaccines to appropriate mucosa‐associated lymphoid tissue. An animal model, based upon the surgical preparation of sterile intestinal ‘loops’ (blind‐ended segments of intestine), was developed to evaluate mucosal and systemic immune responses to enteric vaccines in ruminants. The effectiveness of end‐to‐end intestinal anastomoses was evaluated and fetal surgery did not disrupt normal intestinal function in lambs up to 6–7 months after birth. The immunological competence of Peyer’s patches (PP) within the intestinal ‘loops’ was evaluated with a human adenovirus 5 vector expressing the gD gene of bovine herpesvirus‐1. This vaccine vector induced both mucosal and systemic immune responses when injected into intestinal ‘loops’ of 5–6‐week‐old lambs. An...
Journal of General Virology, Jul 1, 2017
Cell and Tissue Research, Aug 25, 2015
Beta-defensin 103 (DEFB103) shares little homology with 8 other members of the bovine beta-defens... more Beta-defensin 103 (DEFB103) shares little homology with 8 other members of the bovine beta-defensin family and in other species DEFB103 protein has diverse functions, including antimicrobial activity, a chemoattractant for dendritic cells, enhancing epithelial wound repair and regulating hair colour. Expression of the bovine DEFB103 gene was surveyed in 27 tissues and transcript was most abundant in tissues with stratified squamous epithelium. Oral cavity epithelial tissues and nictitating membrane consistently expressed high levels of DEFB103 gene transcript. An age-dependent decrease (P &amp;lt; 0.05) in DEFB103 gene expression was only observed for buccal epithelium when comparing healthy 10- to 14-day-old and 10- to 12-month-old calves. A bovine herpesvirus-1 respiratory infection did, however, significantly (P &amp;lt; 0.05) up-regulate DEFB103 gene expression in the buccal epithelium of 6- to 8-month-old calves. Finally, DEFB103 transcript was low in lymph nodes draining the skin and at the limit of detection in other internal organs such as lung, intestine and kidney. Affinity-purified rabbit antisera to bovine DEFB103 was used to identify cells expressing DEFB103 protein within tissues with stratified squamous epitheliums. DEFB103 protein was most abundant in basal epithelial cells and was present in these cells prior to birth. Beta-defensins have been identified as regulators of dendritic cell (DC) chemokine responses and we observed a close association between DCs and epithelial cells expressing DEFB103 in both the fetus and newborn calf. In conclusion, bovine DEFB103 gene expression is most abundant in stratified squamous epithelium with DEFB103 protein localised to basal epithelial cells. These observations are consistent with proposed roles for DEFB103 in DC recruitment and repair of stratified squamous epithelium.
Journal of Leukocyte Biology, Jun 22, 2006
Journal of General Virology, Oct 1, 2007
Mini-reviews in Medicinal Chemistry, Jun 1, 2008
Proceedings of the World Congress on Genetics Applied to Livestock Production, Aug 21, 2014
Veterinary Immunology and Immunopathology, 2012
We previously reported that CD21(+) B cells purified from bovine blood do not respond to CpG-ODN ... more We previously reported that CD21(+) B cells purified from bovine blood do not respond to CpG-ODN stimulation unless either CD14(+) monocytes or B-cell Activating Factor (BAFF), a cytokine produced by activated monocytes, are present. In this report, we present evidence that CD14(+) monocytes are critical for CpG-specific lymphocyte proliferation within the peripheral blood mononuclear cell (PBMC) population but that this response is not mediated by soluble factors produced by CpG-activated monocytes. We further determine that bovine monocytes stimulated with IFN-γ induce expression of the BAFF gene and that recombinant IFN-γ and BAFF induced robust B cell activation when cultured in the absence of CpG ODN. These data suggest that CpG-stimulated monocytes may indirectly promote B cell activation by promoting release of cytokines and/or other soluble factors from accessory cells which in turn act on CpG-stimulated B cells to promote antigen-independent and T cell independent B cell activation. Understanding the T cell independent signals that induce B cell activation has important implications for understanding B cell development in locations where T cells are limited and in understanding polyclonal B cell activation that may contribute to autoimmune diseases.
Frontiers in Bioinformatics
Antibodies are critical effector molecules of the humoral immune system. Upon infection or vaccin... more Antibodies are critical effector molecules of the humoral immune system. Upon infection or vaccination, populations of antibodies are generated which bind to various regions of the invading pathogen or exogenous agent. Defining the reactivity and breadth of this antibody response provides an understanding of the antigenic determinants and enables the rational development and assessment of vaccine candidates. High-resolution analysis of these populations typically requires advanced techniques such as B cell receptor repertoire sequencing, mass spectrometry of isolated immunoglobulins, or phage display libraries that are dependent upon equipment and expertise which are prohibitive for many labs. High-density peptide microarrays representing diverse populations of putative linear epitopes (immunoarrays) are an effective alternative for high-throughput examination of antibody reactivity and diversity. While a promising technology, widespread adoption of immunoarrays has been limited by ...
Developmental & Comparative Immunology, 2021
The α- and β-adrenergic receptors (ARs) bind the stress hormones epinephrine (E), norepinephrine ... more The α- and β-adrenergic receptors (ARs) bind the stress hormones epinephrine (E), norepinephrine (NE), and dopamine and activate diverse physiological responses. A lack of information on AR gene expression in leukocytes limits our understanding of how stress alters immune function. Quantitative analyses of AR gene expression was completed for bovine leukocytes. Individual leukocyte lineages and subpopulations within lineages were isolated with high-speed cell sorting to facilitate a targeted analysis of AR gene expression. These analyses confirmed all 9 AR genes were expressed in bovine leukocytes with marked differences in AR gene expression when comparing among leukocyte lineages. Furthermore, separation of polymorphonuclear cells into neutrophils and eosinophils revealed these key innate immune cells also differ significantly in AR gene expression. This study provides the first comprehensive survey of AR gene expression in immune cells of any mammalian species and provides insight into conflicting reports that stress can either activate or suppress immune function.
Scientific Reports, 2020
Inter-individual variance in host immune responses following vaccination can result in failure to... more Inter-individual variance in host immune responses following vaccination can result in failure to develop protective immunity leaving individuals at risk for infection in addition to compromising herd immunity. While developing more efficacious vaccines is one strategy to mitigate this problem, predicting vaccine responsiveness prior to vaccination could inform which individuals require adjunct disease management strategies. To identify biomarkers of vaccine responsiveness, a cohort of pigs (n = 120) were vaccinated and pigs representing the high (n = 6; 90th percentile) and low (n = 6; 10th percentile) responders based on vaccine-specific antibody responses following vaccination were further analyzed. Kinase-mediated phosphorylation events within peripheral blood mononuclear cells collected prior to vaccination identified 53 differentially phosphorylated peptides when comparing low responders with high responders. Functional enrichment analysis revealed pro-inflammatory cytokine si...
Scientific Reports, 2020
The mite Varroa destructor is a serious threat to honeybee populations. Selective breeding for Va... more The mite Varroa destructor is a serious threat to honeybee populations. Selective breeding for Varroa mite tolerance could be accelerated by biomarkers within individual bees that could be applied to evaluate a colony phenotype. Previously, we demonstrated differences in kinase-mediated signaling between bees from colonies of extreme phenotypes of mite susceptibility. We expand these findings by defining a panel of 19 phosphorylation events that differ significantly between individual pupae from multiple colonies with distinct Varroa mite tolerant phenotypes. The predictive capacity of these biomarkers was evaluated by analyzing uninfested pupae from eight colonies representing a spectrum of mite tolerance. The pool of biomarkers effectively discriminated individual pupae on the basis of colony susceptibility to mite infestation. Kinome analysis of uninfested pupae from mite tolerant colonies highlighted an increased innate immune response capacity. The implication that differences ...
Applied and Environmental Microbiology, 2019
Dietary interventions to manipulate neonatal gut microbiota have been proposed to generate long-t... more Dietary interventions to manipulate neonatal gut microbiota have been proposed to generate long-term impacts on hosts. Currently, our understanding of the early gut microbiome of neonatal calves is limited to 16S rRNA gene amplicon based microbial profiling, which is a barrier to developing dietary interventions to improve calf gut health. The use of a metagenome sequencing-based approach in the present study revealed high individual animal variation in taxonomic and functional abundance of intestinal microbiome and potential impacts of early microbiome on mucosal immune responses during the preweaning period. During this developmental period, age- and diet-related changes in microbial diversity, richness, density, and the abundance of taxa and functions were observed. A correlation-based approach to further explore the individual animal variation revealed potential enterotypes that can be linked to calf gut health, which may pave the way to developing strategies to manipulate the m...
Veterinary Vaccines: Current Innovations and Future Trends, 2020
Journal of Dairy Science, 2020
Journal of Animal Science, 2019
Mycobacterium avium subsp. Paratuberculosis (MAP) is the causal agent of Johne’s disease (JD), a ... more Mycobacterium avium subsp. Paratuberculosis (MAP) is the causal agent of Johne’s disease (JD), a chronic intestinal disease affecting ruminants worldwide. This study investigated miRNA expression in jejunal intestine (JE) and jejunal lymph nodes (JELN), and the potential regulatory roles of miRNAs during JD progression. JE and JELN tissues were collected from 5 MAP positive (JD subclinical stage) Holstein cows and 5 MAP negative cows. Following miRNA sequencing, bioinformatic processing with a standard pipeline and functional analysis with ClueGo, 272 and 333 miRNAs were identified in JE and JELN, respectively. Compared with MAP negative cows, 13 and 71 miRNAs were differently expressed (DE) (P < 0.05) in MAP infected JE and JELN, respectively. The most up-regulated and down-regulated miRNAs were bta-miR-485 (fold change = 6.18) and bta-miR-451 (fold change = -6.81), and bta-miR-331-5p (fold change = 35.56) and bta-miR-2285bk (fold change = -61.25) in JE and JELN, respectively. I...
Human Vaccines & Immunotherapeutics, 2019
Veterinary Immunology and Immunopathology, 2009
Immunology, 1999
The majority of pathogens enter the body through mucosal surfaces and it is now evident that muco... more The majority of pathogens enter the body through mucosal surfaces and it is now evident that mucosal immunity can provide effective disease protection. However, the induction of mucosal immunity will require efficient targeting of mucosal vaccines to appropriate mucosa‐associated lymphoid tissue. An animal model, based upon the surgical preparation of sterile intestinal ‘loops’ (blind‐ended segments of intestine), was developed to evaluate mucosal and systemic immune responses to enteric vaccines in ruminants. The effectiveness of end‐to‐end intestinal anastomoses was evaluated and fetal surgery did not disrupt normal intestinal function in lambs up to 6–7 months after birth. The immunological competence of Peyer’s patches (PP) within the intestinal ‘loops’ was evaluated with a human adenovirus 5 vector expressing the gD gene of bovine herpesvirus‐1. This vaccine vector induced both mucosal and systemic immune responses when injected into intestinal ‘loops’ of 5–6‐week‐old lambs. An...
Journal of General Virology, Jul 1, 2017
Cell and Tissue Research, Aug 25, 2015
Beta-defensin 103 (DEFB103) shares little homology with 8 other members of the bovine beta-defens... more Beta-defensin 103 (DEFB103) shares little homology with 8 other members of the bovine beta-defensin family and in other species DEFB103 protein has diverse functions, including antimicrobial activity, a chemoattractant for dendritic cells, enhancing epithelial wound repair and regulating hair colour. Expression of the bovine DEFB103 gene was surveyed in 27 tissues and transcript was most abundant in tissues with stratified squamous epithelium. Oral cavity epithelial tissues and nictitating membrane consistently expressed high levels of DEFB103 gene transcript. An age-dependent decrease (P &amp;lt; 0.05) in DEFB103 gene expression was only observed for buccal epithelium when comparing healthy 10- to 14-day-old and 10- to 12-month-old calves. A bovine herpesvirus-1 respiratory infection did, however, significantly (P &amp;lt; 0.05) up-regulate DEFB103 gene expression in the buccal epithelium of 6- to 8-month-old calves. Finally, DEFB103 transcript was low in lymph nodes draining the skin and at the limit of detection in other internal organs such as lung, intestine and kidney. Affinity-purified rabbit antisera to bovine DEFB103 was used to identify cells expressing DEFB103 protein within tissues with stratified squamous epitheliums. DEFB103 protein was most abundant in basal epithelial cells and was present in these cells prior to birth. Beta-defensins have been identified as regulators of dendritic cell (DC) chemokine responses and we observed a close association between DCs and epithelial cells expressing DEFB103 in both the fetus and newborn calf. In conclusion, bovine DEFB103 gene expression is most abundant in stratified squamous epithelium with DEFB103 protein localised to basal epithelial cells. These observations are consistent with proposed roles for DEFB103 in DC recruitment and repair of stratified squamous epithelium.
Journal of Leukocyte Biology, Jun 22, 2006
Journal of General Virology, Oct 1, 2007
Mini-reviews in Medicinal Chemistry, Jun 1, 2008
Proceedings of the World Congress on Genetics Applied to Livestock Production, Aug 21, 2014
Veterinary Immunology and Immunopathology, 2012
We previously reported that CD21(+) B cells purified from bovine blood do not respond to CpG-ODN ... more We previously reported that CD21(+) B cells purified from bovine blood do not respond to CpG-ODN stimulation unless either CD14(+) monocytes or B-cell Activating Factor (BAFF), a cytokine produced by activated monocytes, are present. In this report, we present evidence that CD14(+) monocytes are critical for CpG-specific lymphocyte proliferation within the peripheral blood mononuclear cell (PBMC) population but that this response is not mediated by soluble factors produced by CpG-activated monocytes. We further determine that bovine monocytes stimulated with IFN-γ induce expression of the BAFF gene and that recombinant IFN-γ and BAFF induced robust B cell activation when cultured in the absence of CpG ODN. These data suggest that CpG-stimulated monocytes may indirectly promote B cell activation by promoting release of cytokines and/or other soluble factors from accessory cells which in turn act on CpG-stimulated B cells to promote antigen-independent and T cell independent B cell activation. Understanding the T cell independent signals that induce B cell activation has important implications for understanding B cell development in locations where T cells are limited and in understanding polyclonal B cell activation that may contribute to autoimmune diseases.
Frontiers in Bioinformatics
Antibodies are critical effector molecules of the humoral immune system. Upon infection or vaccin... more Antibodies are critical effector molecules of the humoral immune system. Upon infection or vaccination, populations of antibodies are generated which bind to various regions of the invading pathogen or exogenous agent. Defining the reactivity and breadth of this antibody response provides an understanding of the antigenic determinants and enables the rational development and assessment of vaccine candidates. High-resolution analysis of these populations typically requires advanced techniques such as B cell receptor repertoire sequencing, mass spectrometry of isolated immunoglobulins, or phage display libraries that are dependent upon equipment and expertise which are prohibitive for many labs. High-density peptide microarrays representing diverse populations of putative linear epitopes (immunoarrays) are an effective alternative for high-throughput examination of antibody reactivity and diversity. While a promising technology, widespread adoption of immunoarrays has been limited by ...
Developmental & Comparative Immunology, 2021
The α- and β-adrenergic receptors (ARs) bind the stress hormones epinephrine (E), norepinephrine ... more The α- and β-adrenergic receptors (ARs) bind the stress hormones epinephrine (E), norepinephrine (NE), and dopamine and activate diverse physiological responses. A lack of information on AR gene expression in leukocytes limits our understanding of how stress alters immune function. Quantitative analyses of AR gene expression was completed for bovine leukocytes. Individual leukocyte lineages and subpopulations within lineages were isolated with high-speed cell sorting to facilitate a targeted analysis of AR gene expression. These analyses confirmed all 9 AR genes were expressed in bovine leukocytes with marked differences in AR gene expression when comparing among leukocyte lineages. Furthermore, separation of polymorphonuclear cells into neutrophils and eosinophils revealed these key innate immune cells also differ significantly in AR gene expression. This study provides the first comprehensive survey of AR gene expression in immune cells of any mammalian species and provides insight into conflicting reports that stress can either activate or suppress immune function.
Scientific Reports, 2020
Inter-individual variance in host immune responses following vaccination can result in failure to... more Inter-individual variance in host immune responses following vaccination can result in failure to develop protective immunity leaving individuals at risk for infection in addition to compromising herd immunity. While developing more efficacious vaccines is one strategy to mitigate this problem, predicting vaccine responsiveness prior to vaccination could inform which individuals require adjunct disease management strategies. To identify biomarkers of vaccine responsiveness, a cohort of pigs (n = 120) were vaccinated and pigs representing the high (n = 6; 90th percentile) and low (n = 6; 10th percentile) responders based on vaccine-specific antibody responses following vaccination were further analyzed. Kinase-mediated phosphorylation events within peripheral blood mononuclear cells collected prior to vaccination identified 53 differentially phosphorylated peptides when comparing low responders with high responders. Functional enrichment analysis revealed pro-inflammatory cytokine si...
Scientific Reports, 2020
The mite Varroa destructor is a serious threat to honeybee populations. Selective breeding for Va... more The mite Varroa destructor is a serious threat to honeybee populations. Selective breeding for Varroa mite tolerance could be accelerated by biomarkers within individual bees that could be applied to evaluate a colony phenotype. Previously, we demonstrated differences in kinase-mediated signaling between bees from colonies of extreme phenotypes of mite susceptibility. We expand these findings by defining a panel of 19 phosphorylation events that differ significantly between individual pupae from multiple colonies with distinct Varroa mite tolerant phenotypes. The predictive capacity of these biomarkers was evaluated by analyzing uninfested pupae from eight colonies representing a spectrum of mite tolerance. The pool of biomarkers effectively discriminated individual pupae on the basis of colony susceptibility to mite infestation. Kinome analysis of uninfested pupae from mite tolerant colonies highlighted an increased innate immune response capacity. The implication that differences ...
Applied and Environmental Microbiology, 2019
Dietary interventions to manipulate neonatal gut microbiota have been proposed to generate long-t... more Dietary interventions to manipulate neonatal gut microbiota have been proposed to generate long-term impacts on hosts. Currently, our understanding of the early gut microbiome of neonatal calves is limited to 16S rRNA gene amplicon based microbial profiling, which is a barrier to developing dietary interventions to improve calf gut health. The use of a metagenome sequencing-based approach in the present study revealed high individual animal variation in taxonomic and functional abundance of intestinal microbiome and potential impacts of early microbiome on mucosal immune responses during the preweaning period. During this developmental period, age- and diet-related changes in microbial diversity, richness, density, and the abundance of taxa and functions were observed. A correlation-based approach to further explore the individual animal variation revealed potential enterotypes that can be linked to calf gut health, which may pave the way to developing strategies to manipulate the m...