A5024358466- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Influenza Virus Research Studies
- Inflammasome and immune disorders
- IL-33, ST2, and ILC Pathways
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- Cytomegalovirus and herpesvirus research
- Herpesvirus Infections and Treatments
- Neonatal Respiratory Health Research
- Reproductive System and Pregnancy
- Respiratory viral infections research
- Pancreatic and Hepatic Oncology Research
- Pediatric health and respiratory diseases
- Galectins and Cancer Biology
- Immune responses and vaccinations
- Polyomavirus and related diseases
- Virus-based gene therapy research
- Cystic Fibrosis Research Advances
- Pancreatitis Pathology and Treatment
- Immunodeficiency and Autoimmune Disorders
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Preterm Birth and Chorioamnionitis
- Viral Infections and Vectors
- Occupational and environmental lung diseases
Monash University
2021-2025
Hudson Institute of Medical Research
2021-2025
Murdoch Children's Research Institute
2019-2022
Royal Children's Hospital
2022
The University of Melbourne
2011-2021
Peter Doherty Institute
2015-2021
Age can profoundly affect susceptibility to a broad range of human diseases. Children are more susceptible some infectious diseases such as diphtheria and pertussis, while in others, coronavirus disease 2019 hepatitis A, they protected compared with adults. One explanation is that the composition immune system major contributing factor severity. While most studies have focused on adults, how changes after birth remains poorly understood. Here, using high-dimensional spectral flow cytometry...
Excessive inflammation and tissue damage during severe influenza A virus (IAV) infection can lead to the development of fatal pulmonary disease. Pyroptosis is a lytic pro-inflammatory form cell death executed by pore-forming protein gasdermin D (GSDMD). In this study, we investigated potential role for GSDMD in promoting IAV resulted cleavage vivo vitro lung epithelial cells. Mice genetically deficient (Gsdmd-/-) developed less disease than wildtype mice displayed improved survival outcomes....
Hyperinflammatory responses including the production of NLRP3-dependent interleukin (IL)-1β is a characteristic feature severe and fatal influenza A virus (IAV) infections. The NLRP3 inflammasome has been shown to play temporal role during IAV immune responses, with early protective later detrimental responses. However, specific contribution IL-1β in modulating disease vivo currently not well defined. Here, we identified that activation occurs rapidly following HKx31 H3N2 infection, prior...
The primary function of the monomorphic MHC class Ib molecule Qa-1(b) is to present peptides derived from leader sequences other I molecules for recognition by CD94-NKG2 receptors expressed NK and T cells. Whereas mode peptide presentation its ortholog HLA-E, subsequent CD94-NKG2A, known, molecular basis unclear. We have assessed interaction between CD94-NKG2A shown that they interact with an affinity 17 μM. Furthermore, we determined structure bound sequence peptide, Qdm (AMAPRTLLL), a...
Background Preterm infants are highly vulnerable to infectious disease. While many factors likely contribute this enhanced susceptibility, the immature nature of preterm immune system is postulated as one key factor. Methods In our study, we used high-dimensional flow cytometry and cytokine assays characterise profiles in 25 (range: 30.4-34.1 weeks gestational age) term infant 37-40 cord blood samples. Results We found that exhibit reduced frequencies monocytes, CD56 bright NK cells, CD8+...
Abstract Background Silicosis is a progressive and often fatal occupational lung disease. The NLRP3 inflammasome an innate immune sensor that activated by silica. Accumulating evidence has implicated role for in silicosis pathogenesis. In this study, we mechanistically elucidated the contribution of to silica-induced pulmonary Methods vivo was investigated following intranasal delivery 2 mg silica or diluent alone wildtype, reporter, NLRP3-deficient mice. Protein expression, inflammation,...
Abstract CD4+ T cell responses are crucial for the control of many intracellular pathogens, yet requirements their induction not fully understood. To better understand role that various dendritic (DC) subtypes play in priming, we compared vivo to skin inoculation mice with infectious or UV-inactivated HSV type 1. Localized infection elicited a Th1 response was primed skin-draining lymph nodes involving Ag presentation by migratory dermal and node–resident DC. However, expansion...
Acute and chronic pancreatitis, the latter associated with fibrosis, are multifactorial inflammatory disorders leading causes of gastrointestinal disease-related hospitalization. Despite global health burden currently, there no effective therapeutic agents. In this regard, protease A Disintegrin And Metalloproteinase 17 (ADAM17) mediates responses through shedding bioactive cytokines mediators, including tumor necrosis factor α (TNFα) soluble interleukin (IL)-6 receptor (sIL-6R), which...
CMV-specific, HLA-E–restricted T cell responses to both cognate and self-antigen are fine-tuned by the expression of NK receptors.
Significance Whereas T cells are known to recognize peptides, vitamin B metabolites, or lipid antigens, we identify several nonlipidic small molecules classified as pentamethylbenzofuransulfonates (PBFs) that activate a population of CD1d-restricted natural killer (NKT) cells. This represents breakthrough in the field NKT cell biology. study also reveals previously unknown PBF-reactive healthy individuals with stereotyped receptors paves way for future studies role these immunity, including...
Abstract Objectives Novel host‐targeted therapeutics could treat severe influenza A virus (IAV) infections, with reduced risk of drug resistance. LAT8881 is a synthetic form the naturally occurring C‐terminal fragment human growth hormone. Acting independently hormone receptor, it can reduce inflammation‐induced damage and promote tissue repair in an animal model osteoarthritis. has been assessed clinical trials for treatment obesity neuropathy excellent safety profile. We investigated...
In lung transplant recipients, immunosuppressive medications result in impaired antiviral immunity and a propensity for cytomegalovirus (CMV) reactivation within the allograft. Natural killer (NK) cells play key role to CMV, with an increase proportion of NK expressing activating CD94-NKG2C receptors blood being strong correlate CMV infection. Whether similar NKG2C occurs recipients following allograft if such contribute viral control remains unclear.In this pilot study, we longitudinally...
Hendra virus is an emerging with a geographically broad host reservoir. In humans, causes excessive inflammatory disease of the lung and nervous system. Our current understanding as to how or what factors induce inflammation limited such, there are currently no therapeutic options available for patients who contract virus. Recent studies have identified viral aggregating proteins drivers in influenza A SARS-CoV-2 this study, we sought identify potential proof-of-concept that inflammasome...
Background: People with Cystic Fibrosis (CF) develop pulmonary inflammation, chronic infection and structural lung damage early in life, these manifestations being prevalent among preschool children infants. While immune events are believed to play critical roles shaping the progression, severity disease burden later T cells their subsets poorly studied CF lung, particularly during formative stages of disease. Methods: Using flow cytometry, we analyzed Mucosal Associated Invariant (MAIT)...
Abstract Background Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT8881 is a synthetic 16–amino acid cyclic peptide form naturally occurring C-terminal fragment human growth hormone with therapeutic efficacy against influenza. Shorter linear peptides typically easier to manufacture formulate for delivery than larger peptides. A 6–amino LAT8881, LAT9997, was investigated as potential therapy. Methods LAT9997 evaluated its limit...
Abstract Natural Killer T (NKT) cells detect lipids presented by CD1d. Most studies focus on type I NKT that express semi-invariant αβ cell receptors (TCR) and recognise α-galactosylceramides. However, CD1d also presents structurally distinct to expressing diverse TCRs (type II cells) but our knowledge of the antigens for is limited. An early study identified an agonist, phenyl pentamethyldihydrobenzofuransulfonate (PPBF), which notable its similarity common sulfa-drugs, mechanism NKT-cell...
Abstract The ability of CD4 T cells to give rise specialized follicular helper (TFH) critical initiating appropriate Ab responses is regulated by environmental cues in lymphoid tissues draining the site infection. In this study, we used a skin infection with HSV-1 characterized successive involvement interconnected but distinct lymph nodes (LNs), investigate anatomical diversification virus-specific cell and migratory capacity TFH or their precursors. Whereas Th1 effector expressing...