A5064007273- Mycobacterium research and diagnosis
- Tuberculosis Research and Epidemiology
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Adenosine and Purinergic Signaling
- Cytokine Signaling Pathways and Interactions
- Gut microbiota and health
- Infectious Diseases and Tuberculosis
- MicroRNA in disease regulation
- SARS-CoV-2 and COVID-19 Research
- Urinary Tract Infections Management
- Galectins and Cancer Biology
- interferon and immune responses
- Immune responses and vaccinations
- Extracellular vesicles in disease
- COVID-19 Clinical Research Studies
- Pneumocystis jirovecii pneumonia detection and treatment
- Immune cells in cancer
- Immunodeficiency and Autoimmune Disorders
- COVID-19 Impact on Reproduction
- Microbial infections and disease research
- Complement system in diseases
- Neuroscience of respiration and sleep
- Escherichia coli research studies
- Glycosylation and Glycoproteins Research
University of Technology Sydney
2015-2024
Centenary Institute
2011-2022
The University of Sydney
2010-2021
Bipar
2016
The University of Queensland
2012
Central Clinical Hospital
2005
Colorado State University
1997-2002
Aurobindo Pharma (United States)
1998-2000
The University of Melbourne
1993-1996
The generation of prolonged immunity to Mycobacterium tuberculosis requires not only an antigen‐specific IFN‐γ‐producing T cell response, including both CD4 and CD8 cells, but also the protective granulomatous lesions, whereby close apposition activated cells macrophages acts contain bacterial growth. importance lesion in controlling this immune response limiting tissue damage dissemination has been considered a secondary event but, as present review illustrates, is no less important...
ABSTRACT Evidence showing that neutrophils play a protective role in the host response to infection by different intracellular parasites has been published past few years. We assessed this issue with regard of mice Mycobacterium tuberculosis . found chronic recruitment foci, namely, peritoneal cavity after intraperitoneal and spleen liver intravenous inoculation mycobacteria. However, bacilli were never associated recruited but rather inside macrophages. The administration antineutrophil...
ABSTRACT Immunity to Mycobacterium tuberculosis is dependent upon the generation of a protective gamma interferon (IFN-γ)-producing T-cell response. Recent studies have suggested that interleukin-6 (IL-6) required for induction response and IL-4 may suppress IFN-γ. To evaluate role cytokines IL-6 in pulmonary immunity M. , knockout mice were infected with via aerosol. The absence led an early increase bacterial load concurrent delay However, able contain control growth developed memory...
Genetic variation influences susceptibility to clinical tuberculosis (TB). Activation of the P2X(7) receptor on human macrophages induces killing mycobacteria. We have identified polymorphisms in gene that markedly reduce this killing.To determine if P2X7 are associated with increased risk TB, prevalence four was assessed individuals from Southeast Asia, where majority patients TB our study originate. The association these subsequently investigated two separate case-control cohorts and...
Abstract Cerebral malaria (CM) can be a fatal manifestation of Plasmodium falciparum infection. Using murine models malaria, we found much greater up-regulation number chemokine mRNAs, including those for CXCR3 and its ligands, in the brain during CM (FMCM) than model non-CM. Expression CXCL9 CXCL10 RNA was localized predominantly to cerebral microvessels adjacent glial cells, while expression CCL5 restricted mainly infiltrating lymphocytes. The majority mice deficient were protected from...
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...
Patients with chronic obstructive pulmonary disease (COPD) develop more severe coronavirus (COVID-19); however, it is unclear whether they are susceptible to acute respiratory syndrome 2 (SARS-CoV-2) infection and what mechanisms responsible for disease.
Non-Tuberculous mycobacteria (NTM) are opportunistic environmental bacteria. Globally, NTM incidence is increasing and modeling suggests that, without new interventions, numbers will continue to rise. Effective treatments for infections remain suboptimal. Standard therapy Mycobacterium avium complex, the most commonly isolated NTM, requires a 3-drug regime taken approximately 18 months, with rates of culture conversion reported between 45 70%, high relapse or reinfection at up 60%. New...
Although the essential role of tumor necrosis factor (TNF) in control intracellular bacterial infection is well established, it uncertain whether related cytokines lymphotoxin-alpha (LTalpha3) and lymphotoxin-beta (LTbeta) have independent roles this process. Using C57Bl/6 mice which genes for these been disrupted, we examined relative contribution secreted LTalpha3 membrane-bound LTbeta host response to aerosol Mycobacterium tuberculosis infection. To overcome lack peripheral lymph nodes...
The P2X7 receptor is a ligand-gated cation channel that highly expressed on mononuclear leukocytes and mediates ATP-induced apoptosis killing of intracellular pathogens. There wide variation in function between subjects, explained part by four loss-of-function polymorphisms (R307Q, E496A, I568N, 5′-intronic splice site polymorphism), as well rare mutations. In this study, we report the allele frequencies 11 non-synonymous describe fifth polymorphism gene (1096C → G), which changes Thr357 to...
Abstract TNF is critical for immunity against Mycobacterium tuberculosis infection; however, the relative contributions of soluble and transmembrane forms in this are unknown. Using memTNF mice, which express only form TNF, we have addressed question. Wild-type (WT), TNF−/−, (memTNF) mice were infected with M. by aerosol. TNF−/− developed overwhelming infection extensive pulmonary necrosis died after 33 days. like WT contained bacterial growth over 16 wk, an Ag-specific T cell response,...
Protective immunity against tuberculosis (TB) requires the integrated response of a network lymphocytes. Both gamma interferon (IFN-γ)- and interleukin 17 (IL-17)-secreting CD4(+) T cells have been identified in subjects with latent TB infection during experimental Mycobacterium infection, but contribution Th17 to protective is unclear. To examine their effects vivo, we transferred mycobacterium-specific IL-17- IFN-γ-secreting isolated from M. BCG-immunized IL-12p40(-/-) IFN-γ(-/-) or...
Indoleamine 2,3-dioxygenesae-1 (IDO-1) catalyses the initial, rate-limiting step in tryptophan metabolism, thereby regulating availability and formation of downstream metabolites, including picolinic quinolinic acid. We found that Mycobacterium tuberculosis infection induced marked upregulation IDO-1 expression both human murine macrophages vitro lungs mice following aerosol challenge with M. tuberculosis. The absence dendritic cells enhanced activation mycobacteria-specific T vitro....
Inducible nitric oxide (NO) synthase (iNOS; NOS2) produces NO and related reactive nitrogen species, which are critical effectors of the innate host response required for intracellular killing pathogens such as Mycobacterium tuberculosis Leishmania major. We have identified SPRY domain–containing SOCS (suppressor cytokine signaling) box protein 2 (SPSB2) a novel negative regulator that recruits an E3 ubiquitin ligase complex to polyubiquitinate iNOS, resulting in its proteasomal degradation....
Phagocytosis of apoptotic cells is essential during development and tissue remodeling. Our previous study has shown that the P2X(7) receptor regulates phagocytosis nonopsonized particles bacteria. In this study, we demonstrate also mediates lymphocytes neuronal by human monocyte-derived macrophages under serum-free conditions. ATP inhibited process to a similar extent as observed with cytochalasin D. P2X(7)-transfected HEK-293 acquired ability phagocytose lymphocytes. Injection thymocytes...
We aimed to characterize antimicrobial zinc trafficking within macrophages and determine whether the professional intramacrophage pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) subverts this pathway. Using both Escherichia coli S. Typhimurium, we show that TLR signaling promotes accumulation of vesicular primary human macrophages. Vesicular is delivered E. promote microbial clearance, whereas evades response via pathogenicity island (SPI)-1. Even in absence SPI-1 exporter...
Viral mutations are an emerging concern in reducing SARS-CoV-2 vaccination efficacy. Second-generation vaccines will need to elicit neutralizing antibodies against sites that evolutionarily conserved across the sarbecovirus subgenus. Here, we immunized mice containing a human antibody repertoire with diverse receptor-binding domains (RBDs) identify targeting of vulnerability. Antibodies broad reactivity clade B RBDs class 4 epitope, recurring IGHV/IGKV pairs, were readily elicited but...
Abstract Protective immunity to mycobacterial infections requires activation of the antibacterial mechanisms infected macrophages. It has previously been reported that ATP treatment mycobacteria-infected macrophages induces apoptosis mediated via P2X7 pathway and this leads death both host cell internalized bacilli. We have recently identified a single nucleotide polymorphism in gene (1513A→C), with 1–2% prevalence homozygous state, which codes for nonfunctional receptor. IFN-γ-primed, from...