A5021003953- Tuberculosis Research and Epidemiology
- Immune responses and vaccinations
- Immune Cell Function and Interaction
- Mycobacterium research and diagnosis
- Viral gastroenteritis research and epidemiology
- Salmonella and Campylobacter epidemiology
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- Gut microbiota and health
- Immunodeficiency and Autoimmune Disorders
- Inflammasome and immune disorders
- Pneumocystis jirovecii pneumonia detection and treatment
- Escherichia coli research studies
- Toxoplasma gondii Research Studies
- Clostridium difficile and Clostridium perfringens research
- Parasites and Host Interactions
- Pneumonia and Respiratory Infections
- vaccines and immunoinformatics approaches
- IL-33, ST2, and ILC Pathways
- T-cell and B-cell Immunology
- SARS-CoV-2 and COVID-19 Research
- Pediatric health and respiratory diseases
- Diagnosis and treatment of tuberculosis
- Cytomegalovirus and herpesvirus research
- Infectious Diseases and Mycology
Australian Institute of Tropical Health and Medicine
2014-2025
James Cook University
2014-2025
The University of Melbourne
2010-2023
Peter Doherty Institute
2023
Max Planck Institute for Infection Biology
2013-2019
Charité - Universitätsmedizin Berlin
2007-2013
ABSTRACT Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB), yet its moderate efficacy pulmonary TB calls for improved vaccination strategies. Mucosal BCG generates superior protection in animal models; however, mechanisms of remain elusive. Tissue-resident memory T (T RM ) cells have been implicated protective immune responses viral infections, but role following mycobacterial infection unknown. Using a mouse model TB, we compared and...
Abstract After more than a century since its initial development, Bacille Calmette‐Guérin (BCG) remains the only licensed vaccine against tuberculosis (TB). Subunit boosters are considered viable strategy to enhance BCG efficacy, which often wanes in adolescence. While many studies on booster subunit vaccines have concentrated recombinant proteins, here we developed novel modular peptide‐based platform that is flexible, cold‐chain independent and customizable diverse circumstances...
BackgroundGut bacteria trigger colitis in animal models and are suspected to aggravate inflammatory bowel diseases. We have recently reported that Escherichia coli accumulates murine ileitis exacerbates small intestinal inflammation via Toll-like receptor (TLR) signaling.Methodology Principal FindingsBecause knowledge on shifts the microflora during is limited, we performed a global survey of colon flora C57BL/10 wild-type (wt), TLR2-/-, TLR4-/-, TLR2/4-/- mice treated for seven days with...
The SPI-2 type III secretion system (T3SS) of intracellular Salmonella enterica translocates effector proteins into mammalian cells. Infection antigen-presenting cells results in T3SS-dependent ubiquitination and reduction surface-localized mature MHC class II (mMHCII). We identify the SteD as required sufficient for this process. In Mel Juso cells, localized to Golgi network vesicles containing E3 ubiquitin ligase MARCH8 mMHCII. caused MARCH8-dependent depletion surface One two...
IFN-γ is critical for immunity against infections with intracellular pathogens, such as Salmonella enterica . However, which of the many cell types capable producing controls remains unclear. Using a mouse model systemic infection, we observed that only lack all lymphocytes or CD90 (Thy1) + cells, but not absence T Retinoic acid-related orphan receptor (ROR)-γt–dependent lymphocytes, (NK)1.1 natural killer (NKT), and/or B cells alone, replicated highly susceptible phenotype IFN-γ–deficient...
Background: Resident memory T cells have emerged as key players in the immune response generated against a number of pathogens. Their ability to take residence non-lymphoid peripheral tissues allows for rapid deployment secondary effector responses at site pathogen entry. This provide enhanced regional immunity has gathered much attention, with generation resident being goal many novel vaccines. Objectives: review aimed systematically analyze published literature investigating role human...
IFN-γ is a critical mediator of host defense against Mycobacterium tuberculosis (Mtb) infection. Antigen-specific CD4+ T cells have long been regarded as the main producer in (TB), and cell immunity target current TB vaccine candidates. However, given recent failures such candidate clinical trials, strategies to harness CD4-independent mechanisms protection should be included future design. Here, we reported that noncognate production by Mtb antigen-independent memory CD8+ NK protective...
Inflammasomes promote immunity to microbial pathogens by regulating the function of IL-1-family cytokines such as IL-18 and IL-1β. However, roles for inflammasomes during parasitic helminth infections remain unclear. We demonstrate that mice humans infected with gastrointestinal nematodes display increased secretion, which in Trichuris-infected or worm antigen-treated macrophages co-cultured Trichuris antigens exosome-like vesicles was dependent on NLRP3 inflammasome. NLRP3-deficient...
Mycobacterium tuberculosis (Mtb) primarily resides in the lung but can also persist extrapulmonary sites. Macrophages are considered prime cellular habitat all tissues. Here we demonstrate that Mtb inside adipocytes of fat tissue where it expresses stress-related genes. Moreover, perigonadal Mtb-infected mice disseminated infection when transferred to uninfected animals. Adipose harbors leukocytes addition and other cell types observed induces changes adipose biology depending on stage...
Highlights•Individual T helper cells commit to produce distinct amounts of a given cytokine•The magnitude T-bet expression controls cell's amount IFN-γ production•Single Th1 memory recall the production individual and amounts•Graded bacterial killing by macrophagesSummaryThe probabilistic cytokine genes in differentiated (Th) cell populations remains ill defined. By single-cell analyses mathematical modeling, we show that one stimulation featured stable nonproducers as well producers with...
Tropical infectious diseases inflict an unacceptable burden of disease on humans living in developing countries. While anti-pathogenic drugs have been widely used, they carry a constant threat selecting for resistance. Vaccines offer promising means by which to enhance the global control tropical diseases, but these difficult develop, mostly due complex nature pathogen lifecycles. Here, we present recently developed vaccine candidates five form catalogue, that either entered clinical trials...
It is estimated that two billion people are latently infected with Mycobacterium tuberculosis ( Mtb ), the causative agent of (TB). Latent infection (LTBI) can occur in multiple organs, including lymphatics. The risk LTBI reactivation increases immunocompromised conditions, such as coinfection human immunodeficiency virus (HIV), and during treatment autoimmune diseases organ transplantation. immunological correlates protection against TB, LTBI, remain largely elusive. Here, we used a mouse...
Natural killer (NK) cells are a critical part of the innate immune defense against viral infections and for control tumors. Much less is known about how NK contribute to anti-bacterial immunity. cell-produced interferon gamma (IFN-γ) contributes early exponential replication bacterial pathogens, however regulation these events remains poorly resolved. Using mouse model invasive Salmonellosis, here we report that activation intracellular danger sensor NLRC4 by Salmonella-derived flagellin...
ABSTRACT The rational design of vaccines requires an understanding the contributions individual immune cell subsets to immunity. With this understanding, targeted vaccine delivery approaches and adjuvants can be developed maximize efficiency minimize side effects (S. H. E. Kaufmann et al., Immunity 33:555–577, 2010; T. Ben-Yedidia R. Arnon, Hum. Vaccines 1:95–101, 2005). We have addressed different their ability contribute control clearance facultative intracellular pathogen Salmonella...
Type 2 diabetes (T2D) is a major health problem and considered one of the top 10 diseases leading to death globally. T2D has been widely associated with systemic local inflammatory responses alterations in gut microbiota. Microorganisms, including parasitic worms microbes have exquisitely co-evolved their hosts establish an immunological interaction that essential for formation maintenance balanced immune system, suppression excessive inflammation. Herein we show both prophylactic...
Abstract Antibiotic resistance is a major public health threat, and alternatives to antibiotic therapy are urgently needed. Immunotherapy, particularly the blockade of inhibitory immune checkpoints, leading treatment option in cancer autoimmunity. In this study, we used murine model Salmonella Typhimurium infection investigate whether checkpoint could be applied bacterial infection. We found that T‐cell immunoglobulin ITIM domain (TIGIT) was significantly upregulated on lymphocytes during...
Infection with Mycobacterium tuberculosis (Mtb) is the leading cause of death in human immunodeficiency virus (HIV)+ individuals, particularly Sub-Saharan Africa. Management this deadly co-infection a significant global health challenge that exacerbated by lack efficient vaccines against both Mtb and HIV, as well reliable robust animal models for Mtb/HIV co-infection. Here we describe tractable reproducible mouse model to study reactivation dynamics latent infection following loss CD4+ T...