A5074270668- Tuberculosis Research and Epidemiology
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Mycobacterium research and diagnosis
- T-cell and B-cell Immunology
- interferon and immune responses
- Immunotherapy and Immune Responses
- Immunodeficiency and Autoimmune Disorders
- Immune responses and vaccinations
- Toxoplasma gondii Research Studies
- Cytokine Signaling Pathways and Interactions
- Immune cells in cancer
- Cytomegalovirus and herpesvirus research
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Autophagy in Disease and Therapy
- Cancer Immunotherapy and Biomarkers
- Inflammasome and immune disorders
- Parasites and Host Interactions
- IL-33, ST2, and ILC Pathways
- Infectious Diseases and Tuberculosis
- Influenza Virus Research Studies
- Respiratory viral infections research
- Eosinophilic Esophagitis
- Pneumocystis jirovecii pneumonia detection and treatment
The University of Sydney
2015-2024
The University of Queensland
2024
Westmead Institute for Medical Research
2024
University of Münster
2024
Centenary Institute
2002-2023
Taronga Conservation Society Australia
2020-2023
Shenzhen University
2019-2022
Harry Perkins Institute of Medical Research
2022
Royal Prince Alfred Hospital
2020-2021
National Institute of Allergy and Infectious Diseases
2005-2017
The cytokine interleukin-21 (IL-21) is closely related to IL-2 and IL-15, their receptors all share the common receptor gamma chain, gammac, which mutated in humans with X-linked severe combined immunodeficiency disease (XSCID). We demonstrate that, although mice deficient for IL-21 (IL-21R) have normal lymphoid development, after immunization, these animals higher production of immunoglobulin IgE, but lower IgG1, than wild-type animals. Mice lacking both IL-4 IL-21R exhibited a...
To investigate the role of Toll-like receptor (TLR)9 in immune response to mycobacteria as well its cooperation with TLR2, a known be triggered by several major mycobacterial ligands, we analyzed resistance TLR9−/− TLR2/9 double knockout mice aerosol infection Mycobacterium tuberculosis. Infected but not TLR2−/− displayed defective mycobacteria-induced interleukin (IL)-12p40 and interferon (IFN)-γ responses vivo, common animals, exhibited only minor reductions acute low dose pathogen...
Although interferon γ (IFN-γ) secretion is essential for control of most intracellular pathogens, host survival often also depends on the expression interleukin 10 (IL-10), a cytokine known to counteract IFN-γ effector functions. We analyzed source regulatory IL-10 in mice infected with protozoan parasite Toxoplasma gondii. Unexpectedly, IFN-γ–secreting T-bet+Foxp3− T helper type 1 (Th1) cells were found be major producers these animals. Further analysis revealed that same IL-10+IFN-γγ...
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that caused in part by dysregulated immune response to intestinal flora. The common interleukin (IL)-12/IL-23p40 subunit thought be critical for pathogenesis IBD. We have analyzed role IL-12 versus IL-23 two models Helicobacter hepaticus-triggered T cell-dependent colitis, one involving anti-IL-10R monoclonal antibody treatment infected cell-sufficient hosts, and other CD4+ cell transfer into...
Although CD4 T cells are required for host resistance to Mycobacterium tuberculosis, they may also contribute pathology. In this study, we examine the role of inhibitory receptor PD-1 and its ligand PD-L1 during M. tuberculosis infection. After aerosol exposure, knockout (KO) mice develop high numbers tuberculosis-specific but display markedly increased susceptibility Importantly, show that themselves drive bacterial loads pathology seen in infected KO mice, deficiency is sufficient trigger...
Schistosoma mansoni eggs contain factors that trigger potent Th2 responses in vivo and condition mouse dendritic cells (DCs) to promote lymphocyte differentiation. Using an vitro bystander polarization assay as the readout, we purified identified major Th2-inducing component from soluble egg extract (SEA) secreted T2 ribonuclease, omega-1. The Th2-promoting activity of omega-1 was found be sensitive ribonuclease inhibition did not require MyD88/TRIF signaling DCs. In common with unfractioned...
Type I IFN has been demonstrated to have major regulatory effects on the outcome of bacterial infections. To assess exogenously induced type Mycobacterium tuberculosis infection, we treated pathogen-exposed mice intranasally with polyinosinic-polycytidylic acid condensed poly-l-lysine and carboxymethylcellulose (Poly-ICLC), an agent designed stimulate prolonged, high-level production IFN. Drug-treated, M. tuberculosis-infected WT mice, but not lacking IFN-alphabeta receptor 1 (IFNalphabetaR;...
Abstract Mycobacterium tuberculosis is a virulent intracellular pathogen that survives in macrophages even the presence of an intact adaptive immune response. Type I IFNs have been shown to exacerbate mice and be associated with disease progression infected humans. Nevertheless, mechanisms by which type regulate host response M. infection are poorly understood. In this study, we show induces IFN-related gene expression signature primary human macrophages, dependent on IFN signaling as well...
ABSTRACT The development of more-effective antituberculosis vaccines would assist in the control global problem infection with Mycobacterium tuberculosis . One recently devised vaccination strategy is immunization DNA plasmids encoding individual microbial genes. Using genes for M. secreted proteins MPT64 (23 kDa), Ag85B (30 and ESAT-6 (6 kDa) as candidate antigens, were prepared tested immunogenicity protective efficacy a murine model aerosolized (TB). Intramuscular DNA-64 or DNA-85B...
Abstract Although it is known that IFN-γ-secreting T cells are critical for control of Mycobacterium tuberculosis infection, the contribution IFN-γ produced by NK to host resistance pathogen less well understood. By using cell-deficient RAG−/− mice, we showed M. stimulates cell-dependent production in naive splenic cultures and lungs infected animals. More importantly, common cytokine receptor γ-chain−/−RAG−/− animals deficient cells, p40−/−RAG−/−, or anti-IFN-γ mAb-treated mice displayed...
Abstract To assess the role of Toll-like receptor (TLR) signaling in host resistance to Mycobacterium avium infection, mice deficient TLR adaptor molecule myeloid differentiation factor 88 (MyD88), as well TLR2−/− and TLR4−/− animals, were infected with a virulent strain M. avium, bacterial burdens immune responses compared those wild-type (WT) animals. MyD88−/− failed control acute chronic growth succumbed 9–14 wk postinfection. Infected also showed increased susceptibility, but displayed...
Abstract Dectin-1 is a fungal pattern recognition receptor that binds to β-glucans and triggers cytokine production by facilitating interaction with TLR2 or directly activating spleen tyrosine kinase (Syk). To assess the possible role of in innate response mycobacteria, we used an vitro system which IL-12p40 measured splenic dendritic cells (SpDC) following exposure live Mycobacterium tuberculosis bacilli. Treatment SpDC laminarin glucan phosphate, two molecules known block...
ABSTRACT Mycobacterium tuberculosis possesses agonists for several Toll-like receptors (TLRs), yet mice with single TLR deletions are resistant to acute tuberculosis. MyD88 −/− were used examine whether TLRs play any role in protection against aerogenic M. H37Rv infection. failed control mycobacterial replication and rapidly succumbed. Moreover, expressions of interleukin 12, tumor necrosis factor alpha, gamma interferon, nitric oxide synthase 2 markedly decreased the knockout animals. These...
Eosinophils are frequently found in increased numbers a variety of chronic fibrotic diseases; however, their role the development hepatic fibrosis has not been dissected vivo. Here, we used interleukin-5 (IL-5) knockout (KO) mice to determine whether eosinophils contribute progressive liver that develops response Schistosoma mansoni infection. Although infection intensities were similar C57BL/6 and IL-5 KO mice, average size granulomas was significantly smaller both acutely chronically...
Abstract Although adjuvants are critical vaccine components, their modes of action poorly understood. In this study, we investigated the mechanisms by which heat-killed mycobacteria in CFA promote Th17 CD4+ T cell responses. We found that IL-17 secretion cells following immunization requires MyD88 and IL-1β/IL-1R signaling. Through measurement Ag-specific responses after adoptive transfer OTII cells, confirmed MyD88-dependent signaling controls differentiation rather than simply production...
Tuberculosis (TB) continues to be a critical global health problem, which killed millions of lives each year. Certain circulating cell subsets are thought differentially modulate the host immune response towards Mycobacterium tuberculosis (Mtb) infection, but nature and function these is unclear.Peripheral blood mononuclear cells (PBMC) were isolated from healthy controls (HC), latent infection (LTBI) active then subjected single-cell RNA sequencing (scRNA-seq) using 10 × Genomics platform....
Complement functions as an important host defense system and complement C5 C7 have been implicated in immunopathology of tuberculosis. However, little is known about the role other components tuberculosis.Complement gene expression peripheral blood mononuclear cells tuberculosis patients controls were determined using whole genome transcriptional microarray assays. The mRNA protein levels three C1q components, C1qA, C1qB, C1qC, further validated by qRT-PCR enzyme-linked immunosorbent assay,...
Mycobacterium tuberculosis infection is associated with a spectrum of clinical outcomes, from long-term latent to different manifestations progressive disease. Pro-inflammatory pathways, such as those controlled by IL-1β, have the contrasting potential both prevent disease restricting bacterial replication, and promote inflicting tissue damage. Thus, ultimate contribution individual inflammatory pathways outcome M. remains ambiguous. In this study, we identified naturally-occurring...
Global control of COVID-19 requires broadly accessible vaccines that are effective against SARS-CoV-2 variants. In this report, we exploit the immunostimulatory properties bacille Calmette-Guérin (BCG), existing tuberculosis vaccine, to deliver a vaccination regimen with potent SARS-CoV-2-specific protective immunity. Combination BCG stabilised, trimeric form spike antigen promoted rapid development virus-specific IgG antibodies in blood vaccinated mice, was further augmented by addition...
The hallmark of tuberculosis (TB) is the formation immune cell-enriched aggregates called granulomas. While granulomas are pathologically diverse, their tissue-wide heterogeneity has not been spatially resolved at single-cell level in human tissues. By mapping individual cells every lesion across entire tissue sections, we report that addition to necrotizing granulomas, TB lung contains abundant non-necrotizing leukocyte surrounding areas tissue. These cellular lesions were more diverse...