3,982 results match your criteria: "Doherty Institute for Infection and Immunity[Affiliation]"

Cardiovascular diseases (CVDs), including atherosclerosis, myocardial infarction and heart failure, are the leading causes of morbidity and mortality worldwide. Emerging evidence suggests a crucial role for immune cell dysfunction and inflammation in the progression of this complex set of diseases. Recent advances demonstrate that immune cells, tightly linked to CVD pathogenesis, are sensitive to environmental signals and respond by engaging immunometabolic networks that shape their behavior.

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The Causal Effect of Adult Height on Late-Life Handgrip Strength: The Singapore Chinese Health Study.

J Gerontol A Biol Sci Med Sci

November 2024

Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore.

Background: Adult height has been associated with handgrip strength, which is a surrogate marker of physical frailty. However, it is uncertain if this association is causative or due to confounding bias.

Methods: We evaluated pairwise associations among handgrip strength, adult height, and genetically determined height (using a polygenic score [PGS] for height in a mediation framework and a 2-sample Mendelian randomization approach) by means of a multivariable regression model using a prospective cohort of Chinese living in Singapore.

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Outcomes are presented for a multisite retrospective case series, describing a contemporary cohort of 22 immunocompromised patients with persistent coronavirus disease 2019 (COVID-19) polymerase chain reaction positivity who were retreated with antiviral therapy. For those with data available 14 and 30 days after commencement of antiviral therapy, 41% (9 of 22) and 68% (15 of 22), respectively, cleared COVID-19.

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Article Synopsis
  • Genome-wide association studies (GWAS) have identified genetic links to autoimmune disorders but don't pinpoint causal variants or affected cell types; this research enhances understanding using advanced 3D genomic datasets.
  • By integrating various genomic techniques, the study maps disease-associated variants to likely regulatory effector genes across 57 human cell types, revealing the complex genetic landscape of autoimmune diseases.
  • The investigation identifies both shared and specific genetic pathways, leading to the exploration of squalene synthase as a potential drug target for controlling inflammation in conditions like multiple sclerosis and systemic lupus erythematosus.
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  • Understanding the immune response in acute rheumatic fever (ARF) linked to group A strep (GAS) helps improve disease management and treatment.
  • A notable increase in total IgG3 levels was found in ARF patients, significantly exceeding normal ranges, along with a strong inflammatory response indicated by interleukin-6 and C-reactive protein.
  • The study highlights consistent antibody responses across the disease spectrum, with ARF showing greater intensity and suggests that testing for IgG3 could enhance clinical diagnosis of ARF.
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Dynamin-like GTPase proteins, including myxoma (Mx) and guanylate-binding proteins (GBPs), are among the many interferon stimulated genes induced following viral infections. While studies report that human (h)GBPs inhibit different viruses in vitro, few have convincingly demonstrated that mouse (m)GBPs mediate antiviral activity, although mGBP-deficient mice have been used extensively to define their importance in immunity to diverse intracellular bacteria and protozoa. Herein, we demonstrate that individual (overexpression) or collective (knockout (KO) mice) mGBPs of the chromosome 3 cluster (mGBPchr3) do not inhibit replication of five viruses from different virus families in vitro, nor do we observe differences in virus titres recovered from wild type versus mGBPchr3 KO mice after infection with three of these viruses (influenza A virus, herpes simplex virus type 1 or lymphocytic choriomeningitis virus).

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GALV-KoRV-related retroviruses in diverse Australian and African rodent species.

Virus Evol

July 2024

Life Sciences Discipline, Burnet Institute, 85 Commercial Rd, Melbourne, VIC 3004, Australia.

The enigmatic origins and transmission events of the gibbon ape leukemia virus (GALV) and its close relative the koala retrovirus (KoRV) have been a source of enduring debate. Bats and rodents are each proposed as major reservoirs of interspecies transmission, with ongoing efforts to identify additional animal hosts of GALV-KoRV-related retroviruses. In this study, we identified nine rodent species as novel hosts of GALV-KoRV-related retroviruses.

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Systematic review of knowledge, attitudes, and practices of dairy farmers and consumers towards bovine tuberculosis in low- and middle-income countries.

Prev Vet Med

November 2024

Department of Infectious Diseases, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia; The Nossal Institute for Global Health, The University of Melbourne, Melbourne, Victoria 3000, Australia. Electronic address:

Bovine Tuberculosis (bTB), caused by Mycobacterium bovis, is a neglected zoonotic disease primarily associated with cattle. The incidence of bTB is highest in low-income settings with high cattle density and unpasteurised dairy consumption. Smallholder dairy farming has steadily grown in low- and middle-income countries (LMICs) with limited professional support for adequate bTB surveillance and risk mitigation.

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Persistence of the rebound-competent viral reservoir (RCVR) within the CD4+ T cell compartment of people living with HIV remains a major barrier to HIV cure. Here, we determined the effects of the pan-lymphocyte-depleting monoclonal antibody (mAb) alemtuzumab on the RCVR in SIVmac239-infected rhesus macaques (RM) receiving antiretroviral therapy (ART). Alemtuzumab administered during chronic ART or at the time of ART initiation induced >95% depletion of circulating CD4+ T cells in peripheral blood and substantial CD4+ T cell depletion in lymph nodes.

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This study determined the hepatitis B e antigen (HBeAg) status of people living with chronic hepatitis B (CHB) in Far North Queensland (FNQ), Australia and their age of HBeAg loss. It was hoped that this would provide data to explain the stark difference in the incidence of hepatocellular carcinoma (HCC) between Aboriginal and Torres Strait Islander individuals living with CHB in FNQ, a finding that has been hypothesised to relate to differences in hepatitis B virus genotype. We identified every FNQ resident with CHB, determined their country of birth, their HBeAg status, the age they lost HBeAg and whether they identified as an Aboriginal, a Torres Strait Islander or a non-Indigenous individual.

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Objectives: To compare serological evidence of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with linked coronavirus disease 2019 (COVID-19) case notification data in Victoria, Australia, and to determine SARS-CoV-2 neutralisation activity based on prior infection and vaccination history.

Design, Setting, Participants: Four cross-sectional serological surveys were conducted between 30 June and 31 October 2022 (a period of Omicron BA.4/BA.

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The maternal pregnancy microbiome (including genitourinary and gut) has been linked to important pregnancy/birth and later childhood health outcomes. However, such sampling as part of large population cohort studies is logistically and financially challenging. Many countries routinely collect vaginal or vaginal-rectal swabs in late pregnancy for Group B Streptococcus (GBS) screening, but their utility for population-based research is still unclear.

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Aerobic glycolysis but not GLS1-dependent glutamine metabolism is critical for anti-tumor immunity and response to checkpoint inhibition.

Cell Rep

August 2024

The Peter Doherty Institute for Infection and Immunity and Department of Microbiology and Immunology, University of Melbourne, Parkville, VIC, Australia. Electronic address:

Tumor cells undergo uncontrolled proliferation driven by enhanced anabolic metabolism including glycolysis and glutaminolysis. Targeting these pathways to inhibit cancer growth is a strategy for cancer treatment. Critically, however, tumor-responsive T cells share metabolic features with cancer cells, making them susceptible to these treatments as well.

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Article Synopsis
  • There is a significant need for clinical trials that include infants, children, and adolescents to ensure evidence-based care; this communication discusses three different trial design strategies to address this issue.
  • The three strategies include sequential, parallel, and unified adult-pediatric Bayesian adaptive designs, which allow for better integration of pediatric populations into clinical research.
  • The unified design, exemplified by the SNAP trial, utilizes Bayesian hierarchical models to share data across age groups, enhancing accuracy in assessing treatment safety and efficacy for both children and adults.
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Cell-to-cell interactions revealed by cryo-tomography of a DPANN co-culture system.

Nat Commun

August 2024

Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC, Australia.

DPANN is a widespread and diverse group of archaea characterized by their small size, reduced genome, limited metabolic pathways, and symbiotic existence. Known DPANN species are predominantly obligate ectosymbionts that depend on their host for proliferation. The structural and molecular details of host recognition, host-DPANN intercellular communication, and host adaptation in response to DPANN attachment remain unknown.

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To broadly measure the spectrum of cellular self-antigens for natural killer T cells (NKT), we developed a sensitive lipidomics system to analyze lipids trapped between CD1d and NKT T cell receptors (TCRs). We captured diverse antigen complexes formed in cells from natural endogenous lipids, with or without inducing endoplasmic reticulum (ER) stress. After separating protein complexes with no, low, or high CD1d-TCR interaction, we eluted lipids to establish the spectrum of self-lipids that facilitate this interaction.

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The last decade has seen major advances and growth in internet-based surveillance for infectious diseases through advanced computational capacity, growing adoption of smart devices, increased availability of Artificial Intelligence (AI), alongside environmental pressures including climate and land use change contributing to increased threat and spread of pandemics and emerging infectious diseases. With the increasing burden of infectious diseases and the COVID-19 pandemic, the need for developing novel technologies and integrating internet-based data approaches to improving infectious disease surveillance is greater than ever. In this systematic review, we searched the scientific literature for research on internet-based or digital surveillance for influenza, dengue fever and COVID-19 from 2013 to 2023.

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Coxiella burnetii protein CBU2016 supports CCV expansion.

Pathog Dis

February 2024

Infection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC 3800, Australia.

Coxiella burnetii is a globally distributed obligate intracellular pathogen. Although often asymptomatic, infections can cause acute Q fever with influenza-like symptoms and/or severe chronic Q fever. Coxiella burnetii develops a unique replicative niche within host cells called the Coxiella-containing vacuole (CCV), facilitated by the Dot/Icm type IV secretion system translocating a cohort of bacterial effector proteins into the host.

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High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases.

Cell

August 2024

Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; Center for Influenza Disease and Emergence Response (CIDER), Athens, GA, USA. Electronic address:

Respiratory infections cause significant morbidity and mortality, yet it is unclear why some individuals succumb to severe disease. In patients hospitalized with avian A(H7N9) influenza, we investigated early drivers underpinning fatal disease. Transcriptomics strongly linked oleoyl-acyl-carrier-protein (ACP) hydrolase (OLAH), an enzyme mediating fatty acid production, with fatal A(H7N9) early after hospital admission, persisting until death.

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The immune system plays a crucial role in protecting the body from invading pathogens and maintaining tissue homoeostasis. Maintaining homoeostatic lipid metabolism is an important aspect of efficient immune cell function and when disrupted immune cell function is impaired. There are numerous metabolic diseases whereby systemic lipid metabolism and cellular function is impaired.

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Staphylococcus aureus is a pulmonary pathogen associated with substantial human morbidity and mortality. As vaccines targeting virulence determinants have failed to be protective in humans, other factors are likely involved in pathogenesis. Here we analysed transcriptomic responses of human clinical isolates of S.

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Studies of bacterial adaptation and evolution are hampered by the difficulty of measuring traits such as virulence, drug resistance, and transmissibility in large populations. In contrast, it is now feasible to obtain high-quality complete assemblies of many bacterial genomes thanks to scalable high-accuracy long-read sequencing technologies. To exploit this opportunity, we introduce a phenotype- and alignment-free method for discovering coselected and epistatically interacting genomic variation from genome assemblies covering both core and accessory parts of genomes.

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Hemodialysis is a risk factor for bloodstream infection (SAB). In this single-center study, SAB rates were 56% lower during the monsoonal wet season when patients on hemodialysis receive supervised melioidosis prophylaxis with trimethoprim-sulfamethoxazole. This intervention may reduce SAB rates in high-risk patients; however, further targeted studies are required.

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