ORCID Profile
0000-0002-5119-1711
Current Organisations
Queensland University of Technology
,
Monash University
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Publisher: Wiley
Date: 18-05-2016
DOI: 10.1002/GLIA.23005
Abstract: Under steady-state conditions the central nervous system (CNS) is traditionally thought to be devoid of antigen presenting cells however, putative dendritic cells (DCs) expressing enhanced yellow fluorescent protein (eYFP) are present in the retina and brain parenchyma of CD11c-eYFP mice. We previously showed that these mice carry the Crb1(rd8) mutation, which causes retinal dystrophic lesions therefore we hypothesized that the presence of CD11c-eYFP(+) cells within the CNS may be due to pathology associated with the Crb1(rd8) mutation. We generated CD11c-eYFP Crb1(wt/wt) mice and compared the distribution and immunophenotype of CD11c-eYFP(+) cells in CD11c-eYFP mice with and without the Crb1(rd8) mutation. The number and distribution of CD11c-eYFP(+) cells in the CNS was similar between CD11c-eYFP Crb1(wt/wt) and CD11c-eYFP Crb1(rd8/rd8) mice. CD11c-eYFP(+) cells were distributed throughout the inner retina, and clustered in brain regions that receive input from the external environment or lack a blood-brain barrier. CD11c-eYFP(+) cells within the retina and cerebral cortex of CD11c-eYFP Crb1(wt/wt) mice expressed CD11b, F4/80, CD115 and Iba-1, but not DC or antigen presentation markers, whereas CD11c-eYFP(+) cells within the choroid plexus and pia mater expressed CD11c, I-A/I-E, CD80, CD86, CD103, DEC205, CD8α and CD135. The immunophenotype of CD11c-eYFP(+) cells and microglia within the CNS was similar between CD11c-eYFP Crb1(wt/wt) and CD11c-eYFP Crb1(rd8/rd8) mice however, CD11c and I-A/I-E expression was significantly increased in CD11c-eYFP Crb1(rd8/rd8) mice. This study demonstrates that the overwhelming majority of CNS CD11c-eYFP(+) cells do not display the phenotype of DCs or their precursors and are most likely a subpopulation of microglia. GLIA 2016. GLIA 2016 :1331-1349.
Publisher: Public Library of Science (PLoS)
Date: 20-09-2013
Publisher: Wiley
Date: 27-04-2017
DOI: 10.1002/AR.23601
Abstract: In marsupials that possess a retinal vasculature, the arterial and venous segments, down to the smallest calibre capillaries, have been shown to occur in pairs. This pattern is seen in the marsupial central nervous system (CNS) but not in other tissues in this group or in any tissues in eutherian mammals. The present study aimed to determine if the gray short-tailed opossum (Monodelphis domestica), a south American marsupial, possesses double retinal vessels. Secondly, we investigated the relationship between vessels and astrocytes and microglia, which are known to play pivotal roles in the blood retinal barrier and immune surveillance respectively. Eyes from M. domestica between 2 months and 33 months of age were examined by bright field and fluorescein angiography, resin histology, and wholemount immunostaining. Retinal vessels in this marsupial always occur in closely related pairs with the arteriolar limb usually on the vitread aspect. Branches penetrate the retina to form layers of paired capillaries as far as the outer nuclear layer. Dense networks of GFAP
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 11-08-2021
Publisher: Informa UK Limited
Date: 20-08-2019
DOI: 10.1080/09273948.2019.1646775
Abstract: We report novel differences in mouse corneal DC morphology and density during local and systemic inflammation. Local inflammation was induced by topical application of saline or TLR9 agonist CpG-ODN on abraded C57BL6J mouse corneas. Systemic inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS) in CD11c-YFP mice. Corneal epithelial DCs from uninjured, injured and contralateral eyes were analysed by confocal microscopy. Following local CpG delivery on the injured cornea, the DC density and size increased in both central and peripheral regions. Contralateral uninjured eyes displayed enlarged DC morphology in the central cornea compared to naïve cohorts. After systemic LPS, the size of DCs in the central cornea was lower at 2 hours, returning to baseline after 24 hours. Corneal DCs respond differently in terms of shape and distribution during local and systemic inflammation. These features can serve as
Publisher: American Society for Microbiology
Date: 04-05-2016
Abstract: Urinary tract infection (UTI) is a disease of extremely high incidence in both community and nosocomial settings. UTIs cause significant morbidity and mortality, with approximately 150 million cases globally per year. Uropathogenic Escherichia coli (UPEC) is the primary cause of UTI and is generally treated empirically. However, the rapidly increasing incidence of UTIs caused by multidrug-resistant UPEC strains has led to limited available treatment options and highlights the urgent need to develop alternative treatment and prevention strategies. In this study, we performed a comprehensive analysis to define the regulation, structure, function, and immunogenicity of recently identified UPEC vaccine candidate C1275 (here referred to as IrmA). We showed that the irmA gene is highly prevalent in UPEC, is cotranscribed with the biofilm-associated antigen 43 gene, and is regulated by the global oxidative stress response OxyR protein. Localization studies identified IrmA in the UPEC culture supernatant. We determined the structure of IrmA and showed that it adopts a unique domain-swapped dimer architecture. The dimeric structure of IrmA displays similarity to those of human cytokine receptors, including the interleukin-2 receptor (IL-2R), interleukin-4 receptor (IL-4R), and interleukin-10 receptor (IL-10R) binding domains, and we showed that purified IrmA can bind to their cognate cytokines. Finally, we showed that plasma from convalescent urosepsis patients contains high IrmA antibody titers, demonstrating the strong immunogenicity of IrmA. Taken together, our results indicate that IrmA may play an important role during UPEC infection. IMPORTANCE Uropathogenic E. coli (UPEC) is the primary cause of urinary tract infection (UTI), a disease of major significance to human health. Globally, the incidence of UPEC-mediated UTI is strongly associated with increasing antibiotic resistance, making this extremely common infection a major public health concern. In this report, we describe the regulatory, structural, functional, and immunogenic properties of a candidate UPEC vaccine antigen, IrmA. We demonstrate that IrmA is a small UPEC protein that forms a unique domain-swapped dimer with structural mimicry to several human cytokine receptors. We also show that IrmA binds to IL-2, IL-4, and IL-10, is strongly immunogenic in urosepsis patients, and is coexpressed with factors associated with biofilm formation. Overall, this work suggests a potential novel contribution for IrmA in UPEC infection.
Publisher: Springer Science and Business Media LLC
Date: 11-10-2018
DOI: 10.1038/S41583-018-0070-8
Abstract: Classically, the CNS is described as displaying immune privilege, as it shows attenuated responses to challenge by alloantigen. However, the CNS does show local inflammation in response to infection. Although pathogen access to the brain parenchyma and retina is generally restricted by physiological and immunological barriers, certain pathogens may breach these barriers. In the CNS, such pathogens may either cause devastating inflammation or benefit from immune privilege in the CNS, where they are largely protected from the peripheral immune system. Thus, some pathogens can persist as latent infections and later be reactivated. We review the consequences of immune privilege in the context of CNS infections and ask whether immune privilege may provide protection for certain pathogens and promote their latency.
Publisher: Wiley
Date: 05-03-2009
Publisher: Wiley
Date: 04-2008
Publisher: Wiley
Date: 28-12-2019
DOI: 10.1002/9781118960608.GBM01264.PUB3
Abstract: U.re.a.plas'ma. N.L. fem. n. urea urea Gr. neut. n. plasma anything formed or molded, image, figure N.L. neut. n. Ureaplasma urea form. Tenericutes / Mollicutes / Mycoplasmatales / Mycoplasmataceae / Ureaplasma Bacteria in the genus Ureaplasma , pleomorphic, small (100–800 nm in diameter), primarily coccoid cells, devoid of a cell wall, surrounded by a trilaminar‐membrane structure. Coccobacillary and filamentous forms also occur. These bacteria form exceptionally tiny ( .2 mm) colonies on solid media. Similar to the closely related genus Mycoplasma , ureaplasmas have small (0.75–1.01 Mb) A+T‐rich genomes, use the codon UGA to encode tryptophan, and are nutritionally fastidious. Unlike mycoplasmas they hydrolyze urea rather than glucose or arginine for ATP synthesis. DNA–DNA hybridizations, serotyping of phase‐variable surface‐exposed lipoproteins [the multiple‐banded antigen (MBA)], PCR, and sequencing of the multiple‐banded antigen gene ( mba ), 16S rRNA, and urease genes have defined the species and serovars for this genus. In nature, all species are commensals and/or opportunistic pathogens of vertebrate hosts. Based on the most recent comparative genome analyses, a consensus is emerging that strains associated with humans, the species Ureaplasma urealyticum and Ureaplasma parvum , undergo extensive horizontal gene transfer and may exist collectively as quasi‐species rather than as stable serovars in their native environment. DNA G + C content (mol%) : 25.4–31.9 (complete genome sequences). Type species : Ureaplasma urealyticum Shepard et al. 1974 AL emend. Robertson et al. 2002.
Publisher: American Society for Microbiology
Date: 10-2014
DOI: 10.1128/CMR.00118-13
Abstract: The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis.
Publisher: Wiley
Date: 15-06-2021
DOI: 10.1111/CEO.13954
Publisher: Wiley
Date: 04-2011
Publisher: American Society for Microbiology
Date: 07-2016
DOI: 10.1128/IAI.01546-15
Abstract: Melioidosis, caused by the bacterium Burkholderia pseudomallei , is an often severe infection that regularly involves respiratory disease following inhalation exposure. Intranasal (i.n.) inoculation of mice represents an experimental approach used to study the contributions of bacterial capsular polysaccharide I (CPS I) to virulence during acute disease. We used aerosol delivery of B. pseudomallei to establish respiratory infection in mice and studied CPS I in the context of innate immune responses. CPS I improved B. pseudomallei survival in vivo and triggered multiple cytokine responses, neutrophil infiltration, and acute inflammatory histopathology in the spleen, liver, nasal-associated lymphoid tissue, and olfactory mucosa (OM). To further explore the role of the OM response to B. pseudomallei infection, we infected human olfactory ensheathing cells (OECs) in vitro and measured bacterial invasion and the cytokine responses induced following infection. Human OECs killed % of the B. pseudomallei in a CPS I-independent manner and exhibited an antibacterial cytokine response comprising granulocyte colony-stimulating factor, tumor necrosis factor alpha, and several regulatory cytokines. In-depth genome-wide transcriptomic profiling of the OEC response by RNA-Seq revealed a network of signaling pathways activated in OECs following infection involving a novel group of 378 genes that encode biological pathways controlling cellular movement, inflammation, immunological disease, and molecular transport. This represents the first antimicrobial program to be described in human OECs and establishes the extensive transcriptional defense network accessible in these cells. Collectively, these findings show a role for CPS I in B. pseudomallei survival in vivo following inhalation infection and the antibacterial signaling network that exists in human OM and OECs.
Publisher: American Society for Microbiology
Date: 2017
DOI: 10.1128/CMR.00091-16
Abstract: The human Ureaplasma species are the most frequently isolated microorganisms from the amniotic fluid and placentae of women who deliver preterm and are also associated with spontaneous abortions or miscarriages, neonatal respiratory diseases, and chorioamnionitis. Despite the fact that these microorganisms have been habitually found within placentae of pregnancies with chorioamnionitis, the role of Ureaplasma species as a causative agent has not been satisfactorily explained. There is also controversy surrounding their role in disease, particularly as not all women infected with Ureaplasma spp. develop chorioamnionitis. In this review, we provide evidence that Ureaplasma spp. are associated with diseases of pregnancy and discuss recent findings which demonstrate that Ureaplasma spp. are associated with chorioamnionitis, regardless of gestational age at the time of delivery. Here, we also discuss the proposed major virulence factors of Ureaplasma spp., with a focus on the multiple-banded antigen (MBA), which may facilitate modulation/alteration of the host immune response and potentially explain why only subpopulations of infected women experience adverse pregnancy outcomes. The information presented within this review confirms that Ureaplasma spp. are not simply “innocent bystanders” in disease and highlights that these microorganisms are an often underestimated pathogen of pregnancy.
Publisher: Springer Science and Business Media LLC
Date: 29-06-2023
DOI: 10.1007/S11538-023-01181-0
Abstract: Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease that is driven by immune system-mediated demyelination of nerve axons. While diseases such as cancer, HIV, malaria and even COVID have realised notable benefits from the attention of the mathematical community, MS has received significantly less attention despite the increasing disease incidence rates, lack of curative treatment, and long-term impact on patient well-being. In this review, we highlight existing, MS-specific mathematical research and discuss the outstanding challenges and open problems that remain for mathematicians. We focus on how both non-spatial and spatial deterministic models have been used to successfully further our understanding of T cell responses and treatment in MS. We also review how agent-based models and other stochastic modelling techniques have begun to shed light on the highly stochastic and oscillatory nature of this disease. Reviewing the current mathematical work in MS, alongside the biology specific to MS immunology, it is clear that mathematical research dedicated to understanding immunotherapies in cancer or the immune responses to viral infections could be readily translatable to MS and might hold the key to unlocking some of its mysteries.
Publisher: Wiley
Date: 26-12-2019
DOI: 10.1002/GLIA.23581
Abstract: The central nervous system (CNS) is considered to be immune privileged, owing in part to the absence of major histocompatibility (MHC) class II
Publisher: Springer Science and Business Media LLC
Date: 23-02-2017
DOI: 10.1007/S00424-017-1947-5
Abstract: The eye is a complex sensory organ composed of a range of tissue types including epithelia, connective tissue, smooth muscle, vascular and neural tissue. While some components of the eye require a high level of transparency to allow light to pass through unobstructed, other tissues are characterized by their dense pigmentation, which functions to absorb light and thus control its passage through the ocular structures. Macrophages are present in all ocular tissues, from the cornea at the anterior surface through to the choroid/sclera at the posterior pole. This review will describe the current understanding of the distribution, phenotype, and physiological role of ocular macrophages, and provide a summary of evidence pertaining to their proposed role during pathological conditions.
Publisher: Wiley
Date: 03-2012
Publisher: Elsevier BV
Date: 07-2008
DOI: 10.1016/J.PSCYCHRESNS.2007.08.007
Abstract: It is not known whether the fronto-limbic volume reductions found in adults with established borderline personality disorder (BPD) are present early in the disorder. The aim of the study was to investigate orbitofrontal cortex (OFC), hippoc al and amygdala volumes in a first-presentation teenage BPD s le with minimal exposure to treatment. Groups of 20 BPD patients and 20 healthy control participants underwent magnetic resonance imaging. Hippoc al, amygdala, OFC and whole brain volumes were estimated and compared between the two groups. Analysis of variance revealed reversal of the normal (right>left) asymmetry of OFC grey matter volume in the BPD group, reflecting right-sided OFC grey matter loss in the BPD group compared with control participants. No significant differences were found for amygdala or hippoc al volumes comparing BPD with control participants. We identified OFC but not hippoc al or amygdala volumetric differences early in the course of BPD. Hippoc al and amygdala volume reductions observed in adult BPD s les might develop during the course of the disorder, although longitudinal studies are needed to examine this.
Publisher: Oxford University Press (OUP)
Date: 27-06-2016
Abstract: Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are common infections in humans. Despite the substantial healthcare cost represented by these infections, the human immune response associated with the infection immediately following the onset of symptoms in patients remains largely undefined. We performed a prospective study aimed at defining the milieu of urinary cytokines in adult inpatients in the 24-48 h period immediately following hospital admission for acute cystitis due to UPEC. Urine s les, analyzed using 27-target multiplex protein assays, were used to generate immune profiles for patients and compared to age- and gender-matched healthy controls. The levels of multiple pro-inflammatory cytokines were significantly elevated in urine as a result of infection, an observation consistent with prior findings in murine models and clinical literature. We also identified significant responses for several novel factors not previously associated with the human response to UTI, including Interleukin (IL)-4, IL-7, IL-9, IL-17A, eotaxin, Granulocyte-macrophage colony-stimulating factor (GM-CSF) and several growth factors. These data establish crucial parallels between the human immune response to UPEC and murine model UTI studies, and emphasize the complex but poorly defined nature of the human immune response to UPEC, particularly in the immediate period following the onset of symptoms for acute cystitis.
Publisher: Frontiers Media SA
Date: 07-10-2020
Publisher: American Society for Microbiology
Date: 05-2014
Abstract: Melioidosis is a potentially fatal disease that is endemic to tropical northern Australia and Southeast Asia, with a mortality rate of 14 to 50%. The bacterium Burkholderia pseudomallei is the causative agent which infects numerous parts of the human body, including the brain, which results in the neurological manifestation of melioidosis. The olfactory nerve constitutes a direct conduit from the nasal cavity into the brain, and we have previously reported that B. pseudomallei can colonize this nerve in mice. We have now investigated in detail the mechanism by which the bacteria penetrate the olfactory and trigeminal nerves within the nasal cavity and infect the brain. We found that the olfactory epithelium responded to intranasal B. pseudomallei infection by widespread crenellation followed by disintegration of the neuronal layer to expose the underlying basal layer, which the bacteria then colonized. With the loss of the neuronal cell bodies, olfactory axons also degenerated, and the bacteria then migrated through the now-open conduit of the olfactory nerves. Using immunohistochemistry, we demonstrated that B. pseudomallei migrated through the cribriform plate via the olfactory nerves to enter the outer layer of the olfactory bulb in the brain within 24 h. We also found that the bacteria colonized the thin respiratory epithelium in the nasal cavity and then rapidly migrated along the underlying trigeminal nerve to penetrate the cranial cavity. These results demonstrate that B. pseudomallei invasion of the nerves of the nasal cavity leads to direct infection of the brain and bypasses the blood-brain barrier. IMPORTANCE Melioidosis is a potentially fatal tropical disease that is endemic to northern Australia and Southeast Asia. It is caused by the bacterium Burkholderia pseudomallei , which can infect many organs of the body, including the brain, and results in neurological symptoms. The pathway by which the bacteria can penetrate the brain is unknown, and we have investigated the ability of the bacteria to migrate along nerves that innervate the nasal cavity and enter the frontal region of the brain by using a mouse model of infection. By generating a mutant strain of B. pseudomallei which is unable to survive in the blood, we show that the bacteria rapidly penetrate the cranial cavity using the olfactory (smell) nerve and the trigeminal (sensory) nerve that line the nasal cavity.
No related grants have been discovered for Samantha Dando.