Bernard P Mahon

Bernard P Mahon
National University of Ireland, Maynooth | NUI Maynooth · Institute of Immunology

BSc(Hons), PhD

About

91
Publications
13,590
Reads
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7,944
Citations
Additional affiliations
April 1986 - April 1994
National Institute for Biological Standards and Control
Position
  • Research Officer
Description
  • Polio Expert
January 1999 - December 2012
National University of Ireland, Maynooth
Position
  • Research Director

Publications

Publications (91)
Article
Fasciola hepatica is a trematode worm that causes fascioliasis, a neglected tropical disease in humans and livestock. To gain insight into the host-parasite interactions that facilitate infection, we have investigated the immunomodulatory properties of the parasite's tegumental coat (FhTeg), a major antigen source that is sloughed off and renewed e...
Article
Mesenchymal stromal cells (MSC) have emerged as promising cell therapies for multiple conditions based on demonstrations of their potent immunomodulatory and regenerative capacities in models of inflammatory disease. Understanding the effects of MSC on T cells has dominated the majority of work carried out in this field to date, however, recently a...
Article
Full-text available
Bone-marrow derived mesenchymal stromal cells (MSCs) have potent immunomodulatory and tissue reparative properties, which may be beneficial in the treatment of inflammatory diseases such as COPD. This study examined the mechanisms by which human MSCs protect against elastase induced emphysema. Using a novel human relevant pre-clinical model of emph...
Article
Significance: The mechanisms used by mesenchymal stromal cells (MSCs) in mediating protective effects in chronic models of lung disease are not understood and remain to be elucidated. These findings from in vitro studies highlight an important role for the MSC-derived soluble factors hepatocyte growth factor (HGF) and prostaglandin E2 in promoting...
Article
Full-text available
Burkholderia cepacia complex (Bcc) causes chronic opportunistic lung infections in people with cystic fibrosis (CF) resulting in a gradual lung function decline and, ultimately, patient death. Bcc is a complex of eighteen species and is rarely eradicated once a patient is colonised, therefore vaccination may represent a better therapeutic option. W...
Article
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The immune suppressive and anti-inflammatory capabilities of bone marrow derived mesenchymal stromal cells represents an innovative new tool in regenerative medicine and immune regulation. The potent immune suppressive ability of MSC over T cells, dendritic cells and natural killer cells has been extensively characterised, however the effect of MSC...
Article
Full-text available
Mesenchymal stromal cells (MSC) have well defined immunomodulatory properties including the suppression of lymphocyte proliferation and inhibition of dendritic cell (DC) maturation involving both cell contact and soluble factors. These properties have made MSC attractive candidates for cellular therapy. However, the mechanism underlying these chara...
Article
Umbilical cord tissue represents a unique source of cells with potential for cell therapy applications for multiple diseases. Human umbilical tissue-derived cells (hUTC) are a developmentally early stage, homogenous population of cells that are HLA-ABC dim, HLA-DR negative, and lack expression of co-stimulatory molecules in the unactivated state. T...
Article
The Fourth Expert Meeting of the Mesenchymal Stem Cells in Solid Organ Transplantation (MiSOT) Consortium took place in Barcelona on October 19 and 20, 2012. This meeting focused on the translation of preclinical data into early clinical settings. This position paper highlights the main topics explored on the safety and efficacy of mesenchymal stem...
Article
Acute graft-versus-host disease (aGVHD) is a life-threatening complication following allogeneic haematopoietic stem cell transplantation (HSCT), occurring in up to 30-50% of patients who receive human leucocyte antigen (HLA)-matched sibling transplants. Current therapies for steroid refractory aGVHD are limited, with the prognosis of patients subop...
Conference Paper
This work aims to determine the effect of substituting TiO2for SiO2 in a 0.62SiO2-Na2O-0.24CaO based glass-ceramic scaffold. High temperature X-ray Diffraction (HT-XRD) was used to determine the sintering temperature (700°C). Both optical microscopy and x-ray micotomography was used to determine the average pore size (540-680μm) of each scaffold. C...
Article
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Mesenchymal stromal cells (MSCs) participate in repair of damaged tissues, possess the potential to serve as a useful tool in the drug discovery field and exert immunosuppressive effects as demonstrated by their ability to modulate the immune response. Herein, the roles played by MSC differentiation and/or production of trophic factors involved in...
Data
Full-text available
Acute graft-versus-host disease (aGVHD) is a life-threatening complication following allogeneic haematopoietic stem cell transplantation (HSCT), occurring in up to 30–50% of patients who receive human leucocyte antigen (HLA)-matched sibling transplants. Current therapies for steroid refractory aGVHD are limited, with the prognosis of patients subop...
Article
Full-text available
A series of titanium (Ti) based glasses were formulated (0.62 SiO2–0.14 Na2O–0.24 CaO, with 0.05 mol% TiO2 substitutions for SiO2) to develop glass/ceramic scaffolds for bone augmentation. Glasses were initially characterised using X-ray diffraction (XRD) and particle size analysis, where the starting materials were amorphous with 4.5 μm particles....
Article
Full-text available
Toll-like receptors (TLRs) sense pathogen-associated molecules and respond by inducing cytokines and type I interferon. Here we show that genetic ablation of the E3 ubiquitin ligase Pellino3 augmented the expression of type I interferon but not of proinflammatory cytokines in response to TLR3 activation. Pellino3-deficient mice had greater resistan...
Article
Mesenchymal stem cells (MSCs) inhibit T-cell activation and proliferation but their effects on individual T-cell-effector pathways and on memory versus naïve T cells remain unclear. MSC influence on the differentiation of naïve and memory CD4+ T cells toward the Th17 phenotype was examined. CD4+ T cells exposed to Th17-skewing conditions exhibited...
Article
Adult mesenchymal stem cells possess a remarkably diverse array of immunosuppressive characteristics. The capacity to suppress the regular processes of allogeneic rejection, have allowed the use of tissue mismatched cells as therapeutic approaches in regenerative medicine and as agents of immune deviation. This review describes recent advances in u...
Article
Atopic asthma is an allergic disease typically associated with T(H)2 cytokines. IL-17A is also associated with asthma, through the induction of chemokines. Mucosal CCL28 concentrations correlate with cellular recruitment to inflamed airways and support migration of IgA(+) B cells. Here, a link between IL-17A, CCL28 and IgE-secreting B cell chemotax...
Article
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Despite successful mass vaccination programs, whooping cough remains a significant cause of neonatal mortality. Immunity induced by current vaccines wanes in adolescence, requiring additional immunizations to prevent resurgence. There is a need for a new generation of vaccines capable of conferring long-lasting immunity from birth. Recently, a live...
Article
Full-text available
Allogeneic mesenchymal stem or stromal cells (MSCs) are proposed as cell therapies for degenerative, inflammatory, and autoimmune diseases. The feasibility of allogeneic MSC therapies rests heavily on the concept that these cells avoid or actively suppress the immunological responses that cause rejection of most allogeneic cells and tissues. In thi...
Article
Adult bone marrow-derived mesenchymal stem cells (MSC) possess potent immune modulatory effects which support their possible use as a therapy for immune-mediated disease. MSC induce regulatory T cells (T(reg)) in vitro although the in vivo relevance of this is not clear. This study addressed the hypothesis that adult bone marrow derived-MSC would p...
Article
Virulent Bordetella pertussis, the causative agent of whooping cough, exacerbates allergic airway inflammation in a murine model of ovalbumin (OVA) sensitization. A live genetically attenuated B. pertussis mucosal vaccine, BPZE1, has been developed that evokes full protection against virulent challenge in mice but the effect of this attenuated stra...
Article
Full-text available
A biofilm is an accumulation of micro-organisms and their extracellular products forming a structured community on a surface. Biofilm formation on medical devices has severe health consequences as bacteria growing in this lifestyle are tolerant to both host defence mechanisms and antibiotic therapies. However, silver and zinc ions inhibit the attac...
Article
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Bordetella pertussis is the cause of whooping cough and responsible for 300,000 infant deaths per annum. Current vaccines require 6 months to confer optimal immunity on infants, the population at highest risk. Recently, an attenuated strain of B. pertussis (BPZE1) has been developed to be used as a low-cost, live, intranasal, single-dose vaccine fo...
Article
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Adeno-associated virus serotype 2 (AAV-2) has been developed as a gene therapy vector. Antibody and cell-mediated immune responses to AAV-2 or AAV-2-transfected cells may confound the therapeutic use of such vectors in clinical practice. In one of the most detailed examinations of AAV-2 immunity in humans to date, cell-mediated and humoral immune r...
Article
Adult human mesenchymal stromal or stem cells (MSC) can differentiate into a variety of cell types and are candidate cellular therapeutics in regenerative medicine. Surprisingly, these cells also display multiple potent immunomodulatory capabilities, including allosuppression, making allogeneic cell therapy a possibility. The exact mechanisms invol...
Article
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Hippocampal protein synthesis is dependent upon a number of different molecular and cellular mechanisms that act together to make previously labile memories more stable and resistant to disruption. Both brain-derived neurotrophic factor (BDNF) and extracellular signal-regulated kinase (ERK) are known to play an important role in protein synthesis-d...
Article
Bone morphogenetic proteins (BMPs) are critical morphogens and play key roles in epithelial-mesenchymal transitions (EMTs) during embryogenesis. BMP4 is required for early mesoderm formation and also regulates morphogenesis and epithelial cell differentiation in developing lungs. While, BMP signalling pathways are activated during lung inflammation...
Article
Mesenchymal stem cells (MSC) possess a wide range of immunosuppressive functions. Among these is the ability to inhibit CD4+ T cell proliferation. Dendritic cells (DC) play a role in initiating cell-mediated immunity; however, the immunosuppressive influence of MSC on professional antigen presenting cells remains unclear. DC exposed to TNF-alpha an...
Article
The ability of mesenchymal stem cells (MSC) to suppress alloresponsiveness is poorly understood. Herein, an allogeneic mixed lymphocyte response was used as a model to investigate the mechanisms of MSC-mediated immunomodulation. Human MSC are demonstrated to express the immunosuppressive cytokines hepatocyte growth factor (HGF), interleukin (IL)-10...
Article
Murine mesenchymal stem cells (MSC) have the ability to inhibit allogeneic immune responses. Two different mechanisms, either cell contact-dependent or independent, have been proposed to account for this immunosuppression. The focus of this study was to elucidate the involvement of soluble suppressive factors secreted by murine MSC in an inflammato...
Article
Lipopolysaccharide (LPS) is a potent endotoxin, which produces "sickness behaviours" including loss of weight, loss of interest in food and decreased exploration. LPS has also been shown in some studies to cause deficits in various learning and memory abilities, while in others these LPS-induced learning impairments have been attributed to performa...
Article
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The role of γδ T cells in the regulation of pulmonary inflammation following Bordetella pertussis infection was investigated. Using a well-characterized murine aerosol challenge model, inflammatory events in mice with targeted disruption of the T-cell receptor δ-chain gene (γδ TCR−/− mice) were compared with those in wild-type animals. Early follow...
Article
Mouse models and in vitro cell culture were used to examine airway expression of the mucosal chemokine CCL28. Low levels of constitutively expressed mRNA were observed in transformed murine epithelial cells, but high levels could be induced by stimulation. Cytokines that signal through NF-kappaB, including IL-1beta and TNF-alpha or via JAK-STAT pat...
Article
CCL28 is a mucosal chemokine that attracts eosinophils and T cells via the receptors CCR3 and CCR10. Consequently, it is a candidate mediator of the pathology associated with asthma. This study examined constitutive and induced expression of CCL28 by A549 human airway epithelial-like cells. Real-time RT-PCR and ELISA of cultured cells and supernata...
Article
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There are several characteristics of stem cells that make them unique in comparison with other mammalian cells. First, they exist as unspecialized cells lacking tissue-specific characteristics and they maintain this undifferentiated phenotype until exposed to appropriate signals. Second, they have the capacity for extensive self-renewal. Third, und...
Article
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Adult bone marrow derived mesenchymal stem cells offer the potential to open a new frontier in medicine. Regenerative medicine aims to replace effete cells in a broad range of conditions associated with damaged cartilage, bone, muscle, tendon and ligament. However the normal process of immune rejection of mismatched allogeneic tissue would appear t...
Article
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Infection with influenza virus strongly predisposes an individual to bacterial superinfection, which is often the significant cause of morbidity and mortality during influenza epidemics. Little is known about the immunomodulating properties of the virus that lead to this phenomenon, but the effect of the viral components on the development of immun...
Article
Herein we review recent data that support host tolerance of allogeneic adult mesenchymal stem cells (MSC). Evidence is emerging that donor MSC deploy a very powerful array of mechanisms that allow escape from host allogeneic responses. These mechanisms include limited expression of alloantigen by the stem cell and cell contact-dependent and -indepe...
Article
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The prevalence of asthma and allergic disease has increased in many countries, and there has been speculation that immunization promotes allergic sensitization. Bordetella pertussis infection exacerbates allergic asthmatic responses. We investigated whether acellular pertussis vaccine (Pa) enhanced or prevented B. pertussis-induced exacerbation of...
Article
The prevalence of asthma and allergic disease has increased in many countries and there has been speculation that immunization promotes allergic sensitization. Bordetella pertussis infection exacerbates allergic asthmatic responses. We investigated whether whole-cell pertussis vaccine (Pw) enhanced or prevented B. pertussis induced exacerbation of...
Article
Full-text available
RNA interference is an evolutionary conserved immune response mechanism that can be used as a tool to provide novel insights into gene function and structure. The ability to efficiently deliver small interfering RNA to modulate gene expression in vivo may provide new therapeutic approaches to currently intractable diseases. In vitro, siRNA targetin...
Article
It has been proposed that T helper (Th)2-driven immune deviation in early life can be countered by Th1 inducing childhood infections and that such counter-regulation can protect against allergic asthma. To test whether Th1-inducing infection with Bordetella pertussis protects against allergic asthma using well-characterized murine models. Groups of...
Article
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Loss of antibody reactivity against linear epitopes of parvovirus B19 (B19) capsid proteins VP1 and VP2 occurs after infection; however, it is unclear whether B cell memory is established against linear epitopes. B cell enzyme-linked immunospot assay was used to evaluate B19-specific B cell memory in volunteer donors (n=22). B cell memory is mainta...
Article
Parvovirus B19 infection is a significant cause of fetal death. The aim of this study was to investigate the role of maternal immune status in modulating susceptibility to fetal B19 infection. Peripheral blood was obtained from pregnant women (n = 199) with no clinical evidence of recent B19 infection. Evaluation of ex vivo T cell responses from 14...
Article
Full-text available
Parvovirus B19 (B19) is a human pathogen transmitted to susceptible individuals via respiratory secretions and contaminated blood or blood products. B19 levels in pooled plasma of less than 104 genome equivalents/ml may not be infectious, while those greater than 107/ml are capable of transmitting infection. A World Health Organization (WHO) B19 DN...
Article
The presence of anti-parvovirus B19 (B19V) IgM against viral capsid proteins (VP1 and VP2) has long been used to detect recent infection. The utility of antibodies directed against B19V NS1 protein has received less attention as a serological indicator of recent infection, although anti-B19V NS1 IgG has been associated with persistent infection. To...
Article
There is an urgent requirement for neonatal vaccines that induce effective and long-lasting immune responses at the mucosal surfaces of the gut and respiratory tract. The delay in their development has been due in part to a lack of understanding of the mucosal and neonatal immune systems. This work reviews recent advances in the understanding of th...
Article
Full-text available
Parvovirus B19 is the causative agent of "fifth disease" of childhood. It has been implicated in a variety of conditions, including unsuccessful pregnancy and rheumatoid arthritis, and is a potential contaminant of blood products. There has been little study of immunity to parvovirus B19, and the exact nature of the protective humoral and cell-medi...
Article
Most vaccines used for humans work through humoral immunity, yet many appear to be protective even after specific circulating antibody levels have waned to undetectable levels. Furthermore, it has been difficult to define a serologic correlate of protection against a number of infectious diseases, including those caused by Bordetella pertussis. B....
Article
The role of IFN-gamma in reducing the intracellular load of Bordetella pertussis in murine macrophages in vitro has been examined. The results demonstrate that exposure to IFN-gamma can reduce bacterial load in viable macrophages and that this is associated with production of nitric oxide (NO). These observations provide a mechanism by which IFN-ga...
Article
Pertussis toxin (PT) is a major virulence factor of Bordetella pertussis which exerts a range of effects on the immune system, including the enhancement of IgE, IgA and IgG production, delayed-type hypersensitivity reactions, and the induction of experimental autoimmune diseases. However, the mechanism by which PT mediates adjuvanticity remains to...
Article
The results of phase 3 efficacy trials have shown that acellular and whole-cell pertussis vaccines can confer protection against whooping cough. However, despite the advances in vaccine development, clinical trials have not provided significant new information on the mechanism of protective immunity against Bordetella pertussis. Classical approache...
Article
The explosive technological advances in the fields of immunology and molecular biology in the last 5 years had an enormous impact on the identification of candidate vaccines against diseases, which until a few years ago seemed uncontrollable. Increased knowledge of the immune system has helped to define the mechanisms that underlie successful immun...
Article
The evaluation of vaccines for human use usually requires the development of appropriate animal models and the definition of laboratory correlates of immunity. Traditionally whole cell pertussis vaccines have been controlled by using an active mouse protection test, which measures protection following intracerebral challenge with Bordetella pertuss...
Article
We have used a murine respiratory challenge model to examine the local T cell responses in the lung during infection with Bordetella pertussis. T cells from lung parenchyma and airways of naive and infected mice were refractory to both antigen and mitogen stimulation in the presence of lung macrophages. Furthermore irradiated mononuclear cells from...
Article
Full-text available
Using a murine respiratory challenge model we have previously demonstrated a role for Th1 cells in natural immunity against Bordetella pertussis, but could not rule out a role for antibody. Here we have demonstrated that B. pertussis respiratory infection of mice with targeted disruptions of the genes for the IFN-gamma receptor resulted in an atypi...
Article
Using a murine respiratory infection model, we have demonstrated previously that infection with Bordetella pertussis or immunization with a whole-cell pertussis vaccine induced antigen-specific Th1 cells, which conferred a high level of protection against aerosol challenge. In contrast, immunization with an acellular vaccine, consisting of the B. p...
Article
In studies of the mechanism of immunity to Bordetella pertussis in a murine respiratory infection model, we have previously demonstrated that natural infection of immunization with a whole cell vaccine induces a potent protective immune response, which is mediated by T-helper type-1 (Th1) cells. In contrast an acellular vaccine generates Th2 cells...
Article
Full-text available
The current understanding of the function of CD4+ T helper (Th) cells in immunity to infectious diseases is that Th1 cells, which secrete interleukin (IL)-2 and interferon-gamma, induce cellular immune responses, whereas Th2 cells, which secrete IL-4, IL-5, IL-6, and IL-10, provide helper function for humoral immunity. We have used a panel of polio...
Article
The current understanding of the function of CD4+ T helper (Th) cells in immunity to infectious diseases is that Th1 cells, which secrete interleukin (IL)-2 and interferon-gamma, induce cellular immune responses, whereas Th2 cells, which secrete IL-4, IL-5, IL-6, and IL-10, provide helper function for humoral immunity. We have used a panel of polio...
Article
A fixation and permeabilization procedure using formaldehyde and acetone has been developed which allows immunostaining of intracellular haemoglobin for fluorescence activated cell sorter (FACS) analysis of erythrocytes. The treatment preserves antigenicity and light-scattering properties. Validation of the method was given by the correlation of F...
Article
A method is described for the separation and purification of proteins from complex mixtures of foreign antigens in a form suitable for stimulating T cells in vitro. The technique involves electrophoretic separation of proteins followed by elution, concentration and adsorption of the polypeptide subunits to latex microspheres. Alternatively, where a...
Article
A panel of poliovirus-specific murine CD4+ T-cell clones has been established from both BALB/c (H-2d) and CBA (H-2k) mice immunized with Sabin vaccine strains of poliovirus serotype 1, 2, or 3. T-cell clones were found to be either serotype specific or cross-reactive between two or all three serotypes. Specificity analysis against purified poliovir...