https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45029 Wed 26 Oct 2022 15:43:26 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12574 Wed 11 Apr 2018 16:48:14 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22590 Wed 11 Apr 2018 14:56:27 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:8266 Wed 11 Apr 2018 13:36:02 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13939 Wed 11 Apr 2018 11:31:08 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17958 Wed 11 Apr 2018 09:41:07 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35372 Wed 08 Jul 2020 10:53:44 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43636 Tue 27 Sep 2022 09:39:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50026 Tue 27 Jun 2023 16:47:33 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45298 6 million deaths globally at the time of writing. COVID-19, instigated by the SARS - coronavirus-2 (SARS-CoV-2), causes unprecedented challenges in all facets of our lives, and never before brought scientists of all fields together to focus on this singular topic. While for the past 50 years research have been heavily focused on viruses themselves, we now understand that the host immune responses are just as important in determining the pathogenesis and outcomes of infection. Research in innate immune mechanisms is crucial in understanding all aspects of host antiviral programmes and the mechanisms underpinning virus-host interactions, which can be translated to the development of effective therapeutic avenues. This review summarizes what is known and what remains to be explored in the innate immune responses to influenza viruses and SARS-CoVs, and virus-host interactions in driving disease pathogenesis. This hopefully will encourage discussions and research on the unanswered questions, new paradigms, and antiviral strategies against these emerging infectious pathogens before the next pandemic occurs.]]> Tue 23 May 2023 08:41:55 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42974 Tue 14 May 2024 11:55:54 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43133 Tue 13 Sep 2022 15:14:32 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54163 Tue 06 Feb 2024 13:06:40 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39910 Thu 30 Jun 2022 12:44:37 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45347 Thu 27 Oct 2022 17:08:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51190 Thu 24 Aug 2023 14:39:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39986 Thu 21 Jul 2022 10:44:03 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36808 Thu 04 Nov 2021 10:39:56 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7208 Sat 24 Mar 2018 08:39:57 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7532 Sat 24 Mar 2018 08:38:27 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7533 Sat 24 Mar 2018 08:38:26 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7255 Sat 24 Mar 2018 08:33:49 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15983 50% of asthma-related healthcare costs. New investigations into the pathogenesis of glucocorticoid resistance in severe asthma indicate that pulmonary macrophages may play central roles in promoting airway inflammation, particularly in asthma that is resistant to steroid therapy. Importantly, factors that are linked to the activation of pulmonary macrophages may contribute to glucocorticoid resistance and severe asthma. Here, we review recent advances in understanding the roles of pulmonary macrophages in the mechanisms of glucocorticoid resistance and the pathogenesis of severe asthma. We discuss the role of macrophage phenotype, infection, IFN-γ, LPS, associated signaling pathways, TNF-α, MIF, and other macrophage-associated factors. Understanding the pathogenesis of steroid-resistant severe asthma will contribute to the identification of optimal therapeutic strategies for the effective management of the disease.]]> Sat 24 Mar 2018 08:23:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16017 Sat 24 Mar 2018 08:19:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12382 Sat 24 Mar 2018 08:18:00 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11169 Sat 24 Mar 2018 08:10:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11060 Sat 24 Mar 2018 08:10:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21378 Chlamydia trachomatis infection is increased by oral contraceptives and modulated by sex hormones. We therefore sought to determine the effects of female sex hormones on the innate immune response to C. trachomatis infection. Method of study: ECC-1 endometrial cells, pre-treated with oestradiol or progesterone, were infected with C. trachomatis and the host transcriptome analysed by Illumina Sentrix HumanRef-8 microarray. Primary endocervical epithelial cells, prepared at either the proliferative or secretory phase of the menstrual cycle, were infected with C. trachomatis and cytokine gene expression determined by quantitative RT-PCR analysis. Results: Chlamydia trachomatis yield from progesterone-primed ECC-1 cells was significantly reduced compared with oestradiol-treated cells. Genes upregulated in progesterone-treated and Chlamydia-infected cells only included multiple CC and CXC chemokines, IL-17C, IL-29, IL-32, TNF-α, DEFB4B, LCN2, S100A7-9, ITGAM, NOD2, JAK1, IL-6ST, type I and II interferon receptors, numerous interferon-stimulated genes and STAT6. CXCL10, CXCL11, CX₃CL1 and IL-17C, which were also upregulated in infected secretory-stage primary cells, and there was a trend towards higher levels of immune mediators in infected secretory-phase compared with proliferative-phase cells. Conclusion: Progesterone treatment primes multiple innate immune pathways in hormone-responsive epithelial cells that could potentially increase resistance to chlamydial infection.]]> Sat 24 Mar 2018 08:04:59 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19226 Sat 24 Mar 2018 07:54:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28083 Sat 24 Mar 2018 07:39:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25812 postmortem brain tissue, and later in studies of peripheral blood. The collective body of schizophrenia microarray literature contains apparent inconsistencies between studies, with failures to replicate top hits, in part due to small sample sizes, cohort-specific effects, differences in array types, and other confounders. In an attempt to summarize existing studies of schizophrenia cases and non-related comparison subjects, we performed two mega-analyses of a combined set of microarray data from postmortem prefrontal cortices (n = 315) and from ex-vivo blood tissues (n = 578). We adjusted regression models per gene to remove non-significant covariates, providing best-estimates of transcripts dysregulated in schizophrenia. We also examined dysregulation of functionally related gene sets and gene co-expression modules, and assessed enrichment of cell types and genetic risk factors. The identities of the most significantly dysregulated genes were largely distinct for each tissue, but the findings indicated common emergent biological functions (e.g. immunity) and regulatory factors (e.g., predicted targets of transcription factors and miRNA species across tissues). Our network-based analyses converged upon similar patterns of heightened innate immune gene expression in both brain and blood in schizophrenia. We also constructed generalizable machine-learning classifiers using the blood-based microarray data. Our study provides an informative atlas for future pathophysiologic and biomarker studies of schizophrenia.]]> Sat 24 Mar 2018 07:34:35 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27531 Sat 24 Mar 2018 07:28:58 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22280 in silico and confirmed in luciferase reporter assays. miR-9 function was inhibited with sequence-specific antagomirs. The efficacy of DEX was assessed by quantifying glucocorticoid receptor (GR) cellular localization, protein phosphatase 2A (PP2A) activity, and AHR. Results: Exposure of pulmonary macrophages to IFN-γ/LPS synergistically induced miR-9 expression; reduced levels of its target transcript, protein phosphatase 2 regulatory subunit B (B56) δ isoform; attenuated PP2A activity; and inhibited DEX-induced GR nuclear translocation. Inhibition of miR-9 increased both PP2A activity and GR nuclear translocation in macrophages and restored steroid sensitivity in multiple models of steroid-resistant AHR. Pharmacologic activation of PP2A restored DEX efficacy and inhibited AHR. MiR-9 expression was increased in sputum of patients with neutrophilic but not those with eosinophilic asthma. Conclusion: MiR-9 regulates GR signaling and steroid-resistant AHR. Targeting miR-9 function might be a novel approach for the treatment of steroid-resistant asthma.]]> Sat 24 Mar 2018 07:17:42 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:23760 4 (LXA,sub>4) can also interact with ALX/FPR2 receptors and lead to allosteric inhibition of SAA-initiated epithelial responses (pA₂ 13 nM). During acute exacerbation, peripheral blood SAA levels increased dramatically and were disproportionately increased relative to LXA₄. Human lung macrophages (CD68⁺) colocalized with SAA and GCs markedly increased SAA in vitro (THP-1, pEC₅₀ 43 nM). To determine its direct actions, SAA was administered into murine lung, leading to induction of CXC chemokine ligand 1/2 and a neutrophilic response that was inhibited by 15-epi-LXA₄ but not dexamethasone. Taken together, these findings identify SAA as a therapeutic target for inhibition and implicate SAA as a mediator of GC-resistant lung inflammation that can overwhelm organ protective signaling by lipoxins at ALX/FPR2 receptors.]]> Sat 24 Mar 2018 07:11:08 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38585 in vitro airway epithelial infection models using high multiplicity of infection (MOI) and lacking genome-wide, time course analyses have obscured the role of epithelial innate anti-viral immunity in asthma and COPD. To address this, we developed a low MOI rhinovirus model of differentiated primary epithelial cells obtained from healthy, asthma and COPD donors. Using genome-wide gene expression following infection, we demonstrated that gene expression patterns are similar across patient groups, but that the kinetics of induction are delayed in cells obtained from asthma and COPD donors. Rhinovirus-induced innate immune responses were defined by interferons (type-I, II, and III), interferon response factors (IRF₁, IRF₃, and IRF₇), TLR signaling and NF-κB and STAT₁ activation. Induced gene expression was evident at 24 h and peaked at 48 h post-infection in cells from healthy subjects. In contrast, in cells from donors with asthma or COPD induction was maximal at or beyond 72–96 h post-infection. Thus, we propose that propensity for viral exacerbations of asthma and COPD relate to delayed (rather than deficient) expression of epithelial cell innate anti-viral immune genes which in turns leads to a delayed and ultimately more inflammatory host immune response.]]> Mon 29 Jan 2024 18:03:54 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47533 Mon 23 Jan 2023 12:22:34 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50075 Fri 30 Jun 2023 12:02:10 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37876 Fri 28 May 2021 12:47:02 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33088 H2 cells), their associated cytokines, and eosinophils in the regulation of hallmark features of allergic asthma. Notably, we consider the complexity of type-2 responses and studies that have explored integrated signaling among classical T_H2 cytokines (IL-4, IL-5, and IL-13), which together with CCL11 (eotaxin-1) regulate critical aspects of eosinophil recruitment, allergic inflammation, and airway hyper-responsiveness (AHR). Among our most important findings, we have provided evidence that the initiation of T_H2 responses is regulated by airway epithelial cell-derived factors, including TRAIL and MID1, which promote T_H2 cell development via STAT6-dependent pathways. Further, we highlight studies demonstrating that microRNAs are key regulators of allergic inflammation and potential targets for anti-inflammatory therapy. On the background of T_H2 inflammation, we have demonstrated that innate immune cells (notably, airway macrophages) play essential roles in the generation of steroid-resistant inflammation and AHR secondary to allergen- and pathogen-induced exacerbations. Our work clearly indicates that understanding the diversity and spatiotemporal role of the inflammatory response and its interactions with resident airway cells is critical to advancing knowledge on asthma pathogenesis and the development of new therapeutic approaches.]]> Fri 24 Aug 2018 16:27:29 AEST ]]>