A5018643974- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- COVID-19 Clinical Research Studies
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- Immune responses and vaccinations
- SARS-CoV-2 and COVID-19 Research
- Long-Term Effects of COVID-19
- Tuberculosis Research and Epidemiology
- Asthma and respiratory diseases
- Cholesterol and Lipid Metabolism
- Receptor Mechanisms and Signaling
- COVID-19 Impact on Reproduction
- Inflammasome and immune disorders
- Immune cells in cancer
- Dermatology and Skin Diseases
- Invertebrate Immune Response Mechanisms
- Influenza Virus Research Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- vaccines and immunoinformatics approaches
- Sphingolipid Metabolism and Signaling
- RNA modifications and cancer
- interferon and immune responses
- Respiratory Support and Mechanisms
- Neonatal Respiratory Health Research
Malaghan Institute of Medical Research
2016-2025
National Institute of Allergy and Infectious Diseases
2020-2023
National Institutes of Health
2020-2023
Jiangsu Institute of Parasitic Diseases
2020
University of Otago
2016-2019
Victoria University of Wellington
2016
The poor outcome of the coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, is associated with systemic hyperinflammatory response and immunopathology. Although inflammasome oxidative stress have independently been implicated in COVID-19, it poorly understood whether these two pathways cooperatively contribute to disease severity. Herein, we found an enrichment CD14highCD16- monocytes displaying activation evidenced caspase-1/ASC-speck formation severe COVID-19 patients when compared...
In addition to providing partial protection against pediatric tuberculosis, vaccination with bacille Calmette-Guérin (BCG) has been reported confer nonspecific resistance unrelated pulmonary pathogens, a phenomenon attributed the induction of long-lasting alterations within myeloid cell compartment. Here, we demonstrate that intravenous, but not subcutaneous, inoculation BCG protects human-ACE2 transgenic mice lethal challenge SARS-CoV-2 (SCV2) and results in reduced viral loads...
Cellular necrosis during Mycobacterium tuberculosis (Mtb) infection promotes both immunopathology and bacterial dissemination. Glutathione peroxidase-4 (Gpx4) is an enzyme that plays a critical role in preventing iron-dependent lipid peroxidation–mediated cell death (ferroptosis), process previously implicated the necrotic pathology seen Mtb-infected mice. Here, we document altered GPX4 expression, glutathione levels, peroxidation patients with active assess of this pathway mice genetically...
Type-1 and type-3 interferons (IFNs) are important for control of viral replication; however, less is known about the role Type-2 IFN (IFNγ) in anti-viral immunity. We previously observed that lung infection with Mycobacterium bovis BCG achieved though intravenous (iv) administration provides strong protection against SARS-CoV-2 mice yet drives low levels type-1 IFNs but robust IFNγ. Here we examine ongoing IFNγ responses to pre-established bacterial on disease outcomes two murine models....
The dendritic cell signals required for the in vivo priming of IL-4–producing T cells are unknown. We used RNA sequencing to characterize DCs from skin LN mice exposed two different Th2 stimuli: helminth parasite Nippostrongylus brasiliensis (Nb) and contact sensitizer dibutyl phthalate (DBP)-FITC. Both Nb DBP-FITC induced extensive transcriptional changes that involved multiple DC subsets. Surprisingly, these were highly distinct models, with only a small number genes being similarly...
Influx of eosinophils into the lungs is typically associated with type II responses during allergy and fungal parasitic infections. However, we previously reported that accumulate in lung lesions I inflammatory to Mycobacterium tuberculosis (Mtb) humans, macaques, mice, which they support host resistance. Here show migrate macaques mice as early one week after Mtb exposure. In this influx CCR3 independent instead requires cell-intrinsic expression oxysterol receptor GPR183, highly expressed...
Abstract Oxidative stress triggers ferroptosis, a form of cellular necrosis characterized by iron-dependent lipid peroxidation, and has been implicated in Mycobacterium tuberculosis (Mtb) pathogenesis. We investigated whether Bach1, transcription factor that represses multiple antioxidant genes, regulates host resistance to Mtb. found BACH1 expression is associated clinically with active pulmonary tuberculosis. Bach1 deletion Mtb-infected mice increased glutathione levels Gpx4 inhibit...
Emerging SARS-CoV-2 variants pose a threat to human health worldwide. receptor binding domain (RBD)-based vaccines are suitable candidates for booster vaccines, eliciting focused antibody response enriched virus neutralizing activity. Although RBD proteins manufactured easily, and have excellent stability safety properties, they poorly immunogenic compared the full-length spike protein. We overcome this limitation by engineering subunit vaccine composed of an tandem dimer fused N-terminal...
Helminth endemic regions report lower COVID-19 morbidity and mortality. Here, we show that lung remodeling from a prior infection with lung-migrating helminth, Nippostrongylus brasiliensis, enhances viral clearance survival of human-ACE2 transgenic mice challenged SARS-CoV-2 (SCV2). This protection is associated lymphocytic infiltrate, including increased accumulation pulmonary SCV2-specific CD8+ T cells, anti-CD8 antibody depletion abrogated the N. brasiliensis-mediated reduction in loads....
Viral co-infections have been implicated in worsening tuberculosis (TB) and during the COVID-19 pandemic, global rate of TB-related deaths has increased for first time over a decade. We others previously shown that resolved prior or concurrent influenza A virus infection
Abstract Antigen (Ag)-presenting cells (APC) instruct CD4+ helper T (Th) cell responses, but it is unclear whether different APC subsets contribute uniquely in determining Th differentiation pathogen-specific settings. Here, we use skin-relevant, fluorescently-labeled bacterial, helminth or fungal pathogens to track and characterize the populations that drive responses vivo. All are taken up by a population of IRF4+ dermal migratory dendritic (migDC2) similarly upregulate surface...
Abstract Eosinophils play divergent roles in health and disease, contributing to both immunoregulatory proinflammatory responses. Helminth infection is strongly associated with eosinophilia the induction of type 2 cytokines interleukin (IL)‐5, IL‐4 IL‐13. This study aimed elucidate heterogeneity pulmonary eosinophils response helminth IL‐5, IL‐13 driving eosinophil Using murine model Nippostrongylus brasiliensis ( Nb ), we characterize a subtype eosinophils, defined by high expression CD101,...
Abstract CD4 + T lymphocytes consist of naïve, antigen-specific memory, and memory-phenotype (MP) cell compartments at homeostasis. We recently showed that MP cells exert innate-like effector function during host defense, but whether are functionally heterogeneous and, if so, what signals specify the differentiation subpopulations under homeostatic conditions is still unclear. Here we characterize as consisting T-bet high , low − subsets, with innate, Th1-like activity exclusively associated...
SARS-CoV-2 infection leads to vastly divergent clinical outcomes ranging from asymptomatic fatal disease. Co-morbidities, sex, age, host genetics and vaccine status are known affect disease severity. Yet, how the inflammatory milieu of lung at time exposure impacts control viral replication remains poorly understood. We demonstrate here that immune events in mouse closely preceding significantly impact we identify key innate pathways required limit replication. A diverse set pulmonary...
Severity of COVID-19 is affected by multiple factors; however, it not understood how the inflammatory milieu lung at time SARS-CoV-2 exposure affects control viral replication. Here, we demonstrate that immune events in mouse closely preceding infection affect and identify innate pathways limit Pulmonary stimuli including resolved, antecedent respiratory infections with Staphylococcus aureus or influenza, ongoing pulmonary Mycobacterium tuberculosis infection, ovalbumin/alum-induced asthma,...
Oxysterols (i.e., oxidized cholesterol species) have complex roles in biology. 25-Hydroxycholesterol (25HC), a product of the activity cholesterol-25-hydroxylase (CH25H) on cholesterol, has recently been shown to be broadly antiviral, suggesting therapeutic potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, 25HC can also amplify inflammation and converted by CYP7B1 (cytochrome P450 family 7 subfamily B member 1) 7α,25-dihydroxycholesterol, lipid with...
Abstract Interferons (IFNs) are critical for anti-viral host defence. Type-1 and type-3 IFNs typically associated with early control of viral replication promotion inflammatory immune responses; however, less is known about the role IFNγ in immunity, particularly context SARS-CoV-2. We have previously observed that lung infection attenuated bacteria Mycobacterium bovis BCG achieved though intravenous ( iv ) administration provides strong protection against SARS-CoV-2 (SCV2) disease two mouse...
Macrophage and dendritic cell (DC) populations residing in the intestinal lamina propria (LP) are highly heterogeneous have disparate yet collaborative roles promotion of adaptive immune responses towards antigen. Under steady-state conditions, macrophages efficient at acquiring antigen but non-migratory. In comparison, DC inefficient uptake migrate to mesenteric lymph nodes (mLN) where they present T cells. Whether such distinction transport is maintained under immunostimulatory conditions...
Abstract Early events in the host response to SARS-CoV-2 are thought play a major role determining disease severity. During pulmonary infection, virus encounters both myeloid and epithelioid lineage cells that can either support or restrict pathogen replication as well respond with protective versus detrimental mediators. In addition providing partial protection against pediatric tuberculosis, vaccination bacille Calmette-Guérin (BCG) has been reported confer non-specific resistance...