https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11267 Wed 24 Jul 2013 22:28:44 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22098 Wed 19 Apr 2023 16:41:23 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21992 Bacillus species were identified compared with healthy controls. PCR analyses revealed increased rates of detection of potentially pathogenic bacteria with Haemophilus influenzae detection associated with higher sputum levels of NE and IL-1β, while Streptococcus pneumoniae was more common in male ex-smokers with emphysema and a deficit in diffusion capacity. Conclusion: Non-pathogenic and pathogenic bacteria were altered in the sputum of patients with COPD. These observations highlight the potential to identify treatment and management strategies that both target specific bacterial pathogens and restore the microbial balance, which may lead to reductions in inflammation and subsequent improvements in lung health.]]> Wed 17 Nov 2021 16:31:05 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22109 Wed 11 Apr 2018 16:41:47 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22932 Wed 11 Apr 2018 16:16:56 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22103 Campylobacter jejuni has a broad host range but is especially associated with birds, both domestic and wild. Earlier studies have indicated thrushes of the genus Turdus in Europe to be frequently colonized with C. jejuni, and predominately with host-associated specific genotypes. The European Blackbird Turdus merula, has a large distribution in Europe, including some oceanic islands, and was also introduced to Australia by European immigrants in the 1850s. Methods: The host specificity and temporal stability of European Blackbird C. jejuni was investigated with multilocus sequence typing in a set of isolates collected from Sweden, Australia, and The Azores. Results: Remarkably, we found that the Swedish, Australian, and Azorean isolates were genetically highly similar, despite extensive spatial and temporal isolation. This indicates adaptation, exquisite specificity, and stability in time for European Blackbirds, which is in sharp contrast with the high levels of recombination and mutation found in poultry-related C. jejuni genotypes. Conclusion: The maintenance of host-specific signals in spatially and temporally separated C. jejuni populations suggests the existence of strong purifying selection for this bacterium in European Blackbirds.]]> Wed 11 Apr 2018 16:16:23 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22005 haemophilus influenzae and pharmacological inhibition in mouse and human macrophages augments phagocytosis, the production of reactive oxygen species, and microbicidal activity. Moreover, inhibition of miR-328 in respiratory models of infection, steroid-induced immunosuppression, and smoke-induced emphysema enhances bacterial clearance. Thus, miRNA pathways can be targeted in the lung to enhance host defence against a clinically relevant microbial infection and offer a potential new anti-microbial approach for the treatment of respiratory diseases.]]> Wed 11 Apr 2018 16:14:13 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14161 Wed 11 Apr 2018 16:03:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16827 Wed 11 Apr 2018 16:01:09 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25052 Bacteroidales family S24-7 is a prominent example of one of these groups. Marker gene surveys indicate that members of this family are highly localized to the gastrointestinal tracts of homeothermic animals and are increasingly being recognized as a numerically predominant member of the gut microbiota; however, little is known about the nature of their interactions with the host. Results: Here, we provide the first whole genome exploration of this family, for which we propose the name "Candidatus Homeothermaceae," using 30 population genomes extracted from fecal samples of four different animal hosts: human, mouse, koala, and guinea pig. We infer the core metabolism of "Ca. Homeothermaceae" to be that of fermentative or nanaerobic bacteria, resembling that of related Bacteroidales families. In addition, we describe three trophic guilds within the family, plant glycan (hemicellulose and pectin), host glycan, and a-glucan, each broadly defined by increased abundance of enzymes involved in the degradation of particular carbohydrates. Conclusions: "Ca. Homeothermaceae" representatives constitute a substantial component of the murine gut microbiota, as well as being present within the human gut, and this study provides important first insights into the nature of their residency. The presence of trophic guilds within the family indicates the potential for niche partitioning and specific roles for each guild in gut health and dysbiosis.]]> Wed 11 Apr 2018 15:06:09 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30281 Fbln1c protected against CS-induced airway fibrosis and emphysema-like alveolar enlargement. In experimental COPD, this occurred through disrupted collagen organization and interactions with fibronectin, periostin, and tenascin-c. Genetic inhibition of Fbln1c also reduced levels of pulmonary inflammatory cells and proinflammatory cytokines/chemokines (TNF-a, IL-33, and CXCL1) in experimental COPD. Fbln1c⌿ mice also had reduced airway remodeling in experimental chronic asthma and pulmonary fibrosis. Our data show that Fbln1c may be a therapeutic target in chronic respiratory diseases.]]> Wed 11 Apr 2018 13:33:47 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14152 Wed 11 Apr 2018 12:41:22 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:9558 Wed 11 Apr 2018 12:40:26 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15132 Wed 11 Apr 2018 12:40:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15695 Wed 11 Apr 2018 12:28:11 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30208 Wed 11 Apr 2018 11:33:34 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20766 Wed 11 Apr 2018 11:14:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21292 in vitro. The impact of the anti-angiogenic properties on airways hyperresponsiveness (AHR) was then examined using a murine model of chronic OVA-induced allergic airways disease. Results: The LF-15 and T7 peptides significantly reduced endothelial cell viability and attenuated tube formation in vitro. Mice exposed to OVA+ LF-15 or OVA+T7 also had reduced total lung vascularity and AHR was attenuated compared to mice exposed to OVA alone. T3 peptides reduced cell viability but had no effect on any other parameters. Conclusion: The LF-15 and T7 peptides may be appropriate candidates for use as novel pharmacotherapies due to their small size and anti-angiogenic properties observed in vitro and in vivo.]]> Wed 11 Apr 2018 11:14:04 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14153 Wed 11 Apr 2018 10:56:29 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17025 Wed 11 Apr 2018 10:51:09 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13988 Wed 11 Apr 2018 10:50:22 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24922 Calidris tenuirostris) during both northward and southward migration. Construction of a 33-km long sea-wall was completed in April 2006. We show that shorebird numbers at Saemangeum and two adjacent wetlands decreased by 130000 during northward migration in the next two years and that all species have declined at Saemangeum since completion of the sea-wall. Great Knots were among the most rapidly affected species. Fewer than 5000 shorebirds were recorded at Saemangeum during northward migration in 2014. We found no evidence to suggest that most shorebirds of any species displaced from Saemangeum successfully relocated to other sites in the ROK. Instead, by 2011-13 nearly all species had declined substantially in the ROK since previous national surveys in 1998 and 2008, especially at more heavily reclaimed sites. It is likely that these declines were driven by increased mortality rather than movement to alternate staging sites given that other studies have shown concurrent declines in numbers and survival on the non-breeding grounds. This is the first study in the East Asian-Australasian Flyway to confirm declines of shorebirds at a range of geographical scales following a single reclamation project. The results indicate that if migratory shorebirds are displaced from major staging sites by reclamation they are probably unable to relocate successfully to alternate sites.]]> Wed 11 Apr 2018 10:40:50 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14158 Wed 11 Apr 2018 10:28:43 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:10519 Wed 11 Apr 2018 09:13:51 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21107 Wed 04 Sep 2019 10:31:12 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17324 Tue 31 Mar 2020 08:15:31 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15242 Tue 11 Jun 2019 11:55:23 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23093 Thu 28 Oct 2021 13:04:03 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25846 Thu 28 Oct 2021 12:37:11 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29749 Haemophilus influenzae is a host adapted human mucosal pathogen involved in a variety of acute and chronic respiratory tract infections, including chronic obstructive pulmonary disease and asthma, all of which rely on its ability to efficiently establish continuing interactions with the host. Here we report the characterization of a novel molybdenum enzyme, TorZ/MtsZ that supports interactions of H. influenzae with host cells during growth in oxygen-limited environments. Strains lacking TorZ/MtsZ showed a reduced ability to survive in contact with epithelial cells as shown by immunofluorescence microscopy and adherence/invasion assays. This included a reduction in the ability of the strain to invade human epithelial cells, a trait that could be linked to the persistence of H. influenzae. The observation that in a murine model of H. influenzae infection, strains lacking TorZ/MtsZ were almost undetectable after 72 h of infection, while ∼3.6 × 10³ CFU/mL of the wild type strain were measured under the same conditions is consistent with this view. To understand how TorZ/MtsZ mediates this effect we purified and characterized the enzyme, and were able to show that it is an S- and N-oxide reductase with a stereospecificity for S-sulfoxides. The enzyme converts two physiologically relevant sulfoxides, biotin sulfoxide and methionine sulfoxide (MetSO), with the kinetic parameters suggesting that MetSO is the natural substrate of this enzyme. TorZ/MtsZ was unable to repair sulfoxides in oxidized Calmodulin, suggesting that a role in cell metabolism/energy generation and not protein repair is the key function of this enzyme. Phylogenetic analyses showed that H. influenzae TorZ/MtsZ is only distantly related to the Escherichia coli TorZ TMAO reductase, but instead is a representative of a new, previously uncharacterized clade of molybdenum enzyme that is widely distributed within the Pasteurellaceae family of pathogenic bacteria. It is likely that MtsZ/TorZ has a similar role in supporting host/pathogen interactions in other members of the Pasteurellaceae, which includes both human and animal pathogens.]]> Thu 28 Oct 2021 12:36:21 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26728 Thu 24 Mar 2022 11:33:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29462 IRAKM, PCDH1, ORMDL3/GSDMB, IL-33, CDHR3 and CST1 in airway epithelial cells. Recent studies on epigenetic regulatory factors have further provided novel insights to the field, particularly their effect on regulation of some of the asthma susceptibility genes (e.g. methylation of ADAM33). Among the epigenetic regulatory mechanisms, microRNA networks have been shown to regulate a major portion of post-transcriptional gene regulation. Particularly, miR-19a may have some therapeutic potential.]]> Thu 24 Mar 2022 11:32:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22003 Thu 23 Aug 2018 11:26:32 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15996 Thu 18 Feb 2021 11:21:19 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29938 Thu 03 Feb 2022 12:18:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19859 Thu 01 Aug 2019 17:32:15 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7531 Sat 24 Mar 2018 08:38:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:9358 Sat 24 Mar 2018 08:36:33 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:8182 Sat 24 Mar 2018 08:36:15 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1878 Sat 24 Mar 2018 08:31:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1594 Sat 24 Mar 2018 08:30:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1210 TCI). Following in vitro re-stimulation of lung-draining lymph node cells with MOMP; IFNγ mRNA increased 20-fold in cells from IN immunized animals (compared to non-immunized controls) while IFNγ levels increased 6- to 7-fold in TCI animals. Ten days post challenge non-immunized animals had >7000 IFU in their lungs, IN immunized animals <50 IFU and TCI immunized animals <1500 IFU. Thus, both intranasal and transcutaneous immunization protected mice against respiratory challenge with Chlamydia. The best protection was obtained following IN immunization and correlated with IFNγ production by mononuclear cells in lung-draining LN and MOMP-specific IgA in BAL.]]> Sat 24 Mar 2018 08:28:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13980 Sat 24 Mar 2018 08:24:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13982 Sat 24 Mar 2018 08:24:41 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13806 Sat 24 Mar 2018 08:22:47 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14610 Sat 24 Mar 2018 08:20:47 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15999 Sat 24 Mar 2018 08:19:32 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16016 Sat 24 Mar 2018 08:19:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13324 Sat 24 Mar 2018 08:17:00 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12415 + lymphocytes (Th2 cells) and their cytokines predominate in mild to moderate allergic asthma, whereas severe steroid-resistant asthma has more of a mixed Th2/Th1 phenotype with a Th17 component. Other immune cells, particularly neutrophils, macrophages and dendritic cells, as well structural cells such as epithelial and airway smooth muscle cells also produce disease-associated cytokines in asthma. Increased levels of these immune cells and cytokines have been identified in clinical samples and their potential role in disease demonstrated in studies using mouse models of asthma. Clinical trials with inhibitors of cytokines such as interleukin (IL)-4, -5 and tumour necrosis factor-α have had success in some studies but not others. This may reflect the design of the clinical trials, including treatments regimes and the patient population included in these studies. IL-13, -9 and granulocyte-macrophage colony-stimulating factor are currently being evaluated in clinical trials or preclinically and the outcome of these studies is eagerly awaited. Roles for IL-25, -33, thymic stromal lymphopoietin, interferon-γ, IL-17 and -27 in the regulation of asthma are just emerging, identifying new ways to treat inflammation. Careful interpretation of results from mouse studies will inform the development and application of therapeutic approaches for asthma. The most effective approaches may be combination therapies that suppress multiple cytokines and a range of redundant and disconnected pathways that separately contribute to asthma pathogenesis. Astute application of these approaches may eventually lead to the development of effective asthma therapeutics. Here we review the current state of knowledge in the field.]]> Sat 24 Mar 2018 08:14:54 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11176 Sat 24 Mar 2018 08:14:32 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:10440 106 cfu/mL) was cultured from the sputum of 17 (15%) subjects with stable asthma and was associated with higher total cell counts, proportion and number of neutrophils, sputum IL-8 and 8-isoprostane concentrations. The role of bacteria in potentiating neutrophilic asthma warrants further investigation. Therapies such as antibiotic and antioxidant treatment may be most effective in this sub-group of patients.]]> Sat 24 Mar 2018 08:13:16 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12329 Sat 24 Mar 2018 08:11:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11251 Sat 24 Mar 2018 08:10:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11495 Sat 24 Mar 2018 08:10:23 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11518 Sat 24 Mar 2018 08:10:22 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11164 Sat 24 Mar 2018 08:08:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20803 Sat 24 Mar 2018 08:05:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:18113 Sat 24 Mar 2018 08:04:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20434 −/− C57BL/6 mouse line. The resulting animals exhibited no obvious developmental abnormality, contained normal numbers of granulated MCs in their tissues, and did not compensate for their loss of the membrane tryptase by increasing their expression of other granule proteases. When Prss31-null MCs were activated with a calcium ionophore or by their high affinity IgE receptors, they degranulated in a pattern similar to that of WT MCs. Prss31-null mice had increased baseline airway reactivity to methacholine but markedly reduced experimental chronic obstructive pulmonary disease and colitis, thereby indicating both beneficial and adverse functional roles for the tryptase. In a cigarette smoke-induced model of chronic obstructive pulmonary disease, WT mice had more pulmonary macrophages, higher histopathology scores, and more fibrosis in their small airways than similarly treated Prss31-null mice. In a dextran sodium sulfate-induced acute colitis model, WT mice lost more weight, had higher histopathology scores, and contained more Cxcl-2 and IL-6 mRNA in their colons than similarly treated Prss31-null mice. The accumulated data raise the possibility that inhibitors of this membrane tryptase may provide additional therapeutic benefit in the treatment of humans with these MC-dependent inflammatory diseases.]]> Sat 24 Mar 2018 08:03:21 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19535 Sat 24 Mar 2018 08:02:05 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17439 Sat 24 Mar 2018 08:01:35 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21800 Haemophilus influenzae is one of the most commonly isolated bacteria. The relationship between chronic airway colonisation and the development of steroid-resistant neutrophilic asthma is unclear. Objectives: To investigate the relationship between H influenzae respiratory infection and neutrophilic asthma using mouse models of infection and ovalbumin (OVA)-induced allergic airways disease. Methods: BALB/c mice were intratracheally infected with H influenzae (day 10), intraperitoneally sensitised (day 0) and intranasally challenged (day 12–15) with OVA. Treatment groups were administered dexamethasone intranasally during OVA challenge. Infection, allergic airways disease, steroid sensitivity and immune responses were assessed (days 11, 16 and 21). Results: The combination of H influenzae infection and allergic airways disease resulted in chronic lung infection that was detected on days 11, 16 and 21 (21, 26 and 31 days after infection). Neutrophilic allergic airways disease and T helper 17 cell development were induced, which did not require active infection. Importantly, all features of neutrophilic allergic airways disease were steroid resistant. Toll-like receptor 4 expression and activation of phagocytes was reduced, but most significantly the influx and/or development of phagocytosing neutrophils and macrophages into the airways was inhibited. Conclusions: The combination of infection and allergic airways disease promotes bacterial persistence, leading to the development of a phenotype similar to steroid-resistant neutrophilic asthma and which may result from dysfunction in innate immune cells. This indicates that targeting bacterial infection in steroid-resistant asthma may have therapeutic benefit.]]> Sat 24 Mar 2018 07:59:21 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16896 Sat 24 Mar 2018 07:58:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20869 Sat 24 Mar 2018 07:57:58 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19841 Sat 24 Mar 2018 07:57:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17909 Sat 24 Mar 2018 07:56:41 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16980 Sat 24 Mar 2018 07:55:27 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20982 Sat 24 Mar 2018 07:54:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21119 Sat 24 Mar 2018 07:54:01 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5135 Sat 24 Mar 2018 07:49:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5109 Sat 24 Mar 2018 07:48:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5180 Sat 24 Mar 2018 07:47:49 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5387 Sat 24 Mar 2018 07:43:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27093 Sat 24 Mar 2018 07:40:35 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29786 Tnfsf10^−/−) mice were administered subcutaneous ovalbumin (OVA) followed by oral OVA challenges. In separate experiments, OVA-challenged mice were intraperitoneally administered salmeterol or dexamethasone. Esophageal biopsies from children with EoE revealed increased levels of TRAIL and MID-1 and reduced PP2A activation compared with controls. Tnfsf10^−/− mice were largely protected from esophageal fibrosis, eosinophilic inflammation, and the upregulation of TSLP, IL-5, IL-13, and CCL11 when compared with wild-type mice. Salmeterol administration to wild-type mice with experimental EoE restored PP2A activity and also prevented esophageal eosinophilia, inflammatory cytokine expression, and remodeling, which was comparable to the treatment effect of dexamethasone. TRAIL and PP2A regulate inflammation and fibrosis in experimental EoE, which can be therapeutically modulated by salmeterol.]]> Sat 24 Mar 2018 07:23:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22006 100/FVC. Total lung capacity was increased in HE+DR males. HE males had elevated responses to methacholine. Neonatal hyperoxia alters lung function at mid-adulthood, especially in males.]]> Sat 24 Mar 2018 07:15:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22009 Chlamydia and Haemophilus lung infection-induced SSIAAD. We used these models to investigate the effects of clarithromycin and amoxicillin treatment on immune responses and airways hyper-responsiveness (AHR) in Ova-induced, T helper lymphocyte (Th) 2 -associated steroid-sensitive AAD and infection-induced Th1/Th17-associated SSIAAD compared with dexamethasone treatment. Results: Clarithromycin and amoxicillin had similar antimicrobial effects on infection. Amoxicillin did attenuate some features, but did not broadly suppress either form of AAD. It did restore steroid sensitivity in SSIAAD by reducing infection. In contrast, clarithromycin alone widely suppressed inflammation and AHR in both steroid-sensitive AAD and SSIAAD. This occurred through reductions in Th2 responses that drive steroid-sensitive eosinophilic AAD and tumour necrosis factor a and interleukin 17 responses that induce SSIAAD. Conclusions: Macrolides have broad anti-inflammatory effects in AAD that are likely independent of their antimicrobial effects. The specific responses that are suppressed are dependent upon the responses that dominate during AAD.]]> Sat 24 Mar 2018 07:15:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22024 Sat 24 Mar 2018 07:15:46 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22016 Sat 24 Mar 2018 07:15:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22085 Sat 24 Mar 2018 07:15:16 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21998 Sat 24 Mar 2018 07:14:33 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21996 Sat 24 Mar 2018 07:14:33 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21997 Sat 24 Mar 2018 07:14:33 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22118 Sat 24 Mar 2018 07:13:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22116 Streptococcus pneumoniae (Spn). The effect of Spn IMT on the development of asthma [allergic airways disease (AAD)] was determined in mice. Killed Spn was administered before, during or after ovalbumin sensitization, and the subsequent development of AAD was assessed. IMT attenuated T cell cytokine production, goblet cell hyperplasia, airways hyperresponsiveness (AHR), and eosinophil numbers in the blood, bronchoalveolar lavage fluid and peribronchial tissue. This indicates the potential of Spn as an IMT for asthma.]]> Sat 24 Mar 2018 07:13:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22115 Alloiococcus otitidis has been identified in specimens from patients with chronic otitis media with effusion. Whereas most of those studies employed molecular techniques, we used minor modifications of conventional microbiological methods to isolate and identify A. otitidis in samples obtained from 20/50 (40%) children referred for myringotomy. Alloiococcus otitidis was isolated from 10/22 (45%) Indigenous and 10/28 (36%) non-Indigenous children. This is the first report of isolation of A. otitidis from Australian children with chronic otitis media. All isolates were sensitive to penicillin, but 14/20 (70%) of the isolates were resistant or partially resistant to erythromycin as assessed by the E-test.]]> Sat 24 Mar 2018 07:13:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22114 Chlamydia-induced lung disease was observed 10–15 days after infection, as evidenced by increased bacterial numbers and histopathology in the lung and a reduction in weight gain. After 6 weeks, infection and histopathology had resolved and the rate of weight gain had recovered. Neonatal but not adult infection resulted in significant decreases in interleukin-5 production from helper T cells and by the numbers of eosinophils recruited to the lung in response to ovalbumin exposure. Remarkably, the effects of early-life infection were associated with the generation of both type 1 and 2 ovalbumin-specific helper T-cell cytokine and antibody responses. Furthermore, although neonatal infection significantly attenuated eosinophilia, the generation of the mixed T-cell response exacerbated other hallmark features of asthma: mucus hypersecretion and airway hyperresponsiveness. Moreover, infection prolonged the expression of AAD and these effects were restricted to early-life infection. Conclusions: Early-life chlamydial infection induces a mixed type 1 and 2 T-cell response to antigen, which differentially affects the development of key features of AAD in the adult.]]> Sat 24 Mar 2018 07:13:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22113 Sat 24 Mar 2018 07:13:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22111 Ifn-ε–deficient mice had increased susceptibility to infection of the FRT by the common sexually transmitted infections (STIs) herpes simplex virus 2 and Chlamydia muridarum. Thus, IFN-ε is a potent antipathogen and immunoregulatory cytokine that may be important in combating STIs that represent a major global health and socioeconomic burden.]]> Sat 24 Mar 2018 07:13:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22110 Sat 24 Mar 2018 07:13:17 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22617 Sat 24 Mar 2018 07:12:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22105 Sat 24 Mar 2018 07:10:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22108 Sat 24 Mar 2018 07:10:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22106 Streptococcus pneumoniae induces Tregs that have potential to be harnessed therapeutically for asthma. In this study, mouse models of AAD were used to identify the S. pneumoniae components that have suppressive properties, and the mechanisms underlying suppression were investigated. We tested the suppressive capacity of type-3-polysaccharide (T3P), isolated cell walls, pneumolysoid (Ply) and CpG. When coadministered, T3P + Ply suppressed the development of: eosinophilic inflammation, Th2 cytokine release, mucus hypersecretion, and AHR. Importantly, T3P + Ply also attenuated features of AAD when administered during established disease. We show that NKT cells contributed to the development of AAD and also were suppressed by T3P + Ply treatment. Furthermore, adoptive transfer of NKT cells induced AHR, which also could be reversed by T3P + Ply. T3P + Ply-induced Tregs were essential for the suppression of NKT cells and AAD, which was demonstrated by Treg depletion. Collectively, our results show that the S. pneumoniae components T3P + Ply suppress AAD through the induction of Tregs that blocked the activity of NKT cells. These data suggest that S. pneumoniae components may have potential as a therapeutic strategy for the suppression of allergic asthma through the induction of Tregs and suppression of NKT cells.]]> Sat 24 Mar 2018 07:10:19 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22126 Sat 24 Mar 2018 07:09:58 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22084 Chlamydia trachomatis is a sexually transmitted obligate intracellular pathogen that causes inflammatory reactive arthritis, spondylitis, psoriasiform dermatitis, and conjunctivitis in some individuals after genital infection. The immunologic basis for this inflammatory response in susceptible hosts is poorly understood. As ZAP-70^W163C–mutant BALB/c (SKG) mice are susceptible to spondylo-arthritis after systemic exposure to microbial β-glucan, we undertook the present study to compare responses to infection with Chlamydia muridarum in SKG mice and BALB/c mice. Methods: After genital or respiratory infection with C muridarum, conjunctivitis and arthritis were assessed clinically, and eye, skin, and joint specimens were analyzed histologically. Chlamydial major outer membrane protein antigen–specific responses were assessed in splenocytes. Treg cells were depleted from FoxP3-DTR BALB/c or SKG mice, and chlamydial DNA was quantified by polymerase chain reaction. Results: Five weeks after vaginal infection with live C muridarum, arthritis, spondylitis, and psoriasiform dermatitis developed in female SKG mice, but not in BALB/c mice. Inflammatory bowel disease did not occur in mice of either strain. The severity of inflammatory disease was correlated with C muridarum inoculum size and vaginal burden postinoculation. Treatment with combination antibiotics starting 1 day postinoculation prevented disease. Chlamydial antigen was present in macrophages and spread from the infection site to lymphoid organs and peripheral tissue. In response to chlamydial antigen, production of interferon-γ and interleukin-17 was impaired in T cells from SKG mice but tumor necrosis factor (TNF) responses were exaggerated, compared to findings in T cells from BALB/c mice. Unlike previous observations in arthritis triggered by β-glucan, no autoantibodies developed. Accelerated disease triggered by depletion of Treg cells was TNF dependent. Conclusion: In the susceptible SKG strain, Chlamydia-induced reactive arthritis develops as a result of deficient intracellular pathogen control, with antigen-specific TNF production upon dissemination of antigen, and TNF-dependent inflammatory disease.]]> Mon 06 Aug 2018 11:11:21 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22044 Chlamydia, Haemophilus influenzae and Streptococcus pneumoniae in early life may promote permanent deleterious changes in immunity, lung structure, and function that predispose to, or increase the severity of chronic respiratory diseases in later life. For example, these infections increase immune responses, which drive subsequent asthma pathogenesis. Targeting the pathways involved with specific inhibitors or agonists may prevent these consequences of early-life infection. Vaccination and immunomodulatory therapies that control the infections and their sequelae may also be efficacious.]]> Mon 01 Feb 2016 13:04:15 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22119 Listeria monocytogenes causes a life-threatening disease known as listeriosis. The mechanism by which L. monocytogenes invades mammalian cells is not fully understood, but the processes involved may provide targets to prevent and treat listeriosis. Here, for the first time, we have identified the insulin-like growth factor II receptor (IGFIIR; also known as the cation-independent mannose 6-phosphate receptor ^CIM6PR or CD222) as a novel receptor for binding and invasion of Listeria species. Random peptide phage display was employed to select a peptide sequence by panning with immobilized L. monocytogenes cells; this peptide sequence corresponds to a sequence within the mannose 6-phosphate binding site of the IGFIIR. All Listeria spp. specifically bound the labeled peptide but not a control peptide, which was demonstrated using fluorescence spectrophotometry and fluorescence-activated cell sorting. Further evidence for binding of the receptor by L. monocytogenes and L. innocua was provided by affinity purification of the bovine IGFIIR from fetal calf serum by use of magnetic beads coated with cell preparations of Listeria spp. as affinity matrices. Adherence to and invasion of mammalian cells by L. monocytogenes was significantly inhibited by both the synthetic peptide and mannose 6-phosphate but not by appropriate controls. These observations indicate a role for the IGFIIR in the adherence and invasion of L. monocytogenes of mammalian cells, perhaps in combination with known mechanisms. Ligation of IGFIIR by L. monocytogenes may be a novel mechanism that contributes to the regulation of infectivity, possibly in combination with other mechanisms.]]> Fri 12 Feb 2016 15:22:05 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30274 Streptococcus pneumoniae and vaccination are inversely associated with asthma. Studies in animal models demonstrate that airway administration of S. pneumoniae (live or killed), or its vaccines or components, suppresses the characteristic features of asthma in mouse models of allergic airway disease (AAD). These components could be developed into immunoregulatory therapies. S. pneumoniae components are recognized by Toll-like receptors (TLR) 2 and TLR4, and both induce inflammatory cell responses through the adaptor protein myeloid differentiation primary response gene 88 (MyD88). The involvement of TLR2, TLR4 and MyD88 in the pathogenesis of AAD and asthma is incompletely understood, and has not been studied in S. pneumoniae-mediated suppression of AAD. We investigated the role of TLR2, TLR4 and MyD88 in the development of AAD and S. pneumoniae-mediated suppression of AAD. Methods and Findings: OVA-induced AAD and killed S. pneumoniae-mediated suppression of AAD were assessed in wild-type, TLR2 ^-/-, TLR4 ^-/-, TLR2/4 ^-/- and MyD88 ^-/- BALB/c mice. During OVA-induced AAD, TLR2, TLR4 and MyD88 were variously involved in promoting eosinophil accumulation in bronchoalveolar lavage fluid and blood, and T-helper type (Th)2 cytokine release from mediastinal lymph node T cells and splenocytes. However, all were required for the induction of airways hyperresponsiveness (AHR). In S. pneumoniae-mediated suppression of AAD, TLR2, TLR4 and MyD88 were variously involved in the suppression of eosinophilic and splenocyte Th2 responses but all were required for the reduction in AHR. Conclusions: These results highlight important but complex roles for TLR2, TLR4 and MyD88 in promoting the development of OVA-induced AAD, but conversely in the S. pneumoniae-mediated suppression of AAD, with consistent and major contributions in both the induction and suppression of AHR. Thus, TLR signaling is likely required for both the development of asthma and the suppression of asthma by S. pneumoniae, and potentially other immunoregulatory therapies.]]> Fri 01 Apr 2022 09:28:59 AEDT ]]>