A5058245844- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Tryptophan and brain disorders
- Inflammasome and immune disorders
- Cell death mechanisms and regulation
- Gut microbiota and health
- Salmonella and Campylobacter epidemiology
- interferon and immune responses
- Pediatric health and respiratory diseases
- Mitochondrial Function and Pathology
- Legionella and Acanthamoeba research
- Liver Disease Diagnosis and Treatment
- RNA Research and Splicing
- Metabolomics and Mass Spectrometry Studies
- vaccines and immunoinformatics approaches
- Vibrio bacteria research studies
- Trace Elements in Health
- Escherichia coli research studies
- Respiratory viral infections research
- Influenza Virus Research Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Peter Doherty Institute
2016-2024
The University of Melbourne
2016-2024
Walter and Eliza Hall Institute of Medical Research
2017
Monash University
2017
Hudson Institute of Medical Research
2017
Robert Koch Institute
2010-2014
In recent years, human dendritic cells (DCs) could be subdivided into CD304+ plasmacytoid DCs (pDCs) and conventional (cDCs), the latter encompassing CD1c+, CD16+, CD141+ DC subsets. To date, low frequency of these in blood has essentially prevented functional studies defining their specific contribution to antigen presentation. We have established a protocol for an effective isolation pDC cDC subsets high purity. Using this approach, we show that are only express chemokine receptor XCR1...
Whereas CD4 + T cells conventionally mediate antitumor immunity by providing help to CD8 cells, recent clinical studies have implied an important role for cytotoxic in cancer immunity. Using orthotopic melanoma model, we provide a detailed account of antitumoral cell responses and their regulation major histocompatibility complex class II (MHC II) the skin. Intravital imaging revealed prominent interactions with tumor debris-laden MHC host antigen-presenting that accumulated around nests,...
Cross-presentation of antigen by dendritic cells (DCs) to CD8+ T is a fundamentally important mechanism in the defense against pathogens and tumors. Due lack an appropriate lineage marker, cross-presenting DCs mouse are provisionally classified as "Batf3-IRF8-Id2-dependent DCs" or "CD8+ spleen, "CD103+CD11b- periphery. We have now generated mAb XCR1, chemokine receptor which specifically expressed on subpopulation double-negative spleen. Using this antibody, we determined that only XCR1+CD8+...
Programmed cell death contributes to host defense against pathogens. To investigate the relative importance of pyroptosis, necroptosis, and apoptosis during Salmonella infection, we infected mice macrophages deficient for diverse combinations caspases-1, -11, -12, -8 receptor interacting serine/threonine kinase 3 (RIPK3). Loss caspase-8-driven apoptosis, or necroptosis had minor impact on control. However, combined deficiency these pathways caused loss bacterial control in their macrophages,...
Current subunit vaccines are incapable of inducing Ag-specific CD8(+) T cell cytotoxicity needed for the defense certain infections and therapy neoplastic diseases. In experimental vaccines, cytotoxic responses can be elicited by targeting Ag into cross-presenting dendritic cells (DC), but almost all available systems use target molecules also expressed on other thus lack desired specificity. present work, we induced to XCR1, a chemokine receptor exclusively murine human DC. Targeting with...
DCs often require stimulation from CD4+ T cells to propagate CD8+ cell responses, but precisely how help optimizes the priming capacity of and why this appears differ between varying types immunity remains unclear. We show that upon HSV-1 skin infection depended on receiving both IFN-α/β provide IL-15. This was not an additive effect resulted amplifying DC production IL-15 in response IFN-α/β. also observed increased innate reversed helper dependence stimulus, rather than themselves,...
Antiviral CD8+ T cell immunity depends on the integration of various contextual cues, but how antigen-presenting cells (APCs) consolidate these signals for decoding by remains unclear. Here, we describe gradual interferon-α/interferon-β (IFNα/β)-induced transcriptional adaptations that endow APCs with capacity to rapidly activate regulators p65, IRF1 and FOS after CD4+ cell-mediated CD40 stimulation. While responses operate through broadly used signaling components, they induce a unique set...
Respiratory infections cause significant morbidity and mortality, yet it is unclear why some individuals succumb to severe disease. In patients hospitalized with avian A(H7N9) influenza, we investigated early drivers underpinning fatal Transcriptomics strongly linked oleoyl-acyl-carrier-protein (ACP) hydrolase (OLAH), an enzyme mediating fatty acid production, after hospital admission, persisting until death. Recovered had low OLAH expression throughout hospitalization. High levels were also...
Naïve CD8 + T cells need to undergo a complex and coordinated differentiation program gain the capacity control virus infections. This not only involves acquisition of effector functions, but also regulates development subset into long-lived protective memory cells. Microbiota-derived metabolites have recently gained interest for their influence on cells, much remains unclear about role in cell differentiation. In this study, we investigated G protein-coupled receptors (GPR)41 GPR43 that can...
In the past, lack of lineage markers confounded classification dendritic cells (DC) in intestine and impeded a full understanding their location function. We have recently shown that chemokine receptor XCR1 is marker for cross-presenting DC spleen. Now, we provide evidence intestinal XCR1(+) largely, but not fully, overlap with CD103(+) CD11b(-) DC, hypothesized correlate "cross-presenting DC" intestine, are selectively dependent development on transcription factor Batf3. located villi...
Legionella pneumophila is the causative agent of Legionnaires' disease, a potentially fatal lung infection. Alveolar macrophages support intracellular replication L. pneumophila, however contributions other immune cell types to bacterial killing during infection are unclear. Here, we used recently described methods characterise major inflammatory cells in after acute respiratory mice with pneumophila. We observed that numbers alveolar rapidly decreased coincident rapid infiltration by...
The impact of respiratory virus infections on global health is felt not just during a pandemic, but endemic seasonal pose an equal and ongoing risk severe disease. Moreover, vaccines antiviral drugs are always effective or available for many viruses. We investigated how induction appropriate antigen-independent innate immunity in the upper airways can prevent spread infection to vulnerable lower airways. Activation TLR2, when restricted nasal turbinates, resulted prompt immune–driven...
Tissue-resident memory T cells (TRM cells) are key elements of tissue immunity. Here, we investigated the role regulator cell receptor and cytokine signaling, Ptpn2, in formation function TRM skin. Ptpn2-deficient CD8+ displayed a marked defect generating CD69+ CD103+ response to herpes simplex virus type 1 (HSV-1) skin infection. This was accompanied by reduction proportion KLRG1− precursor transcriptional bias toward terminal differentiation. Of note, forced expression KLRG1 sufficient...
Resolution of virus infections depends on the priming virus-specific CD8+ T cells by dendritic (DC). While this process requires major histocompatibility complex (MHC) class I-restricted antigen presentation DC, relative contribution to cell infected DC is less clear. We have addressed question in context a peripheral infection with herpes simplex 1 (HSV). Assessing endogenous, polyclonal HSV-specific response, we found that effective vivo depended presence subsets specialized...
In the past, lack of lineage markers confounded classification dendritic cells (DC) in intestine and impeded a full understanding their location function. We have recently shown that chemokine receptor XCR1 is marker for cross-presenting DC spleen. Now we provide evidence intestinal XCR1+ largely, but not fully, overlap with CD103+ CD11b- DC, hypothesized correlate cross-presenting DC intestine, are selectively dependent development on transcription factor Batf3. located villi epithelial...
Abstract Dendritic cells (DC) are pivotal for initiating adaptive immunity, a process triggered by the activation of DC via pathogen products or damage. Here, we describe an additional layer to this process, essential when pathogen-derived signals alone cannot directly achieve full activation. Immunisation with sporozoites from Plasmodium leads CD8 T cell priming in complex response that is initiated collaboration between conventional type 1 (cDC1) and γδ cells. We unveil role Vγ1 + cells,...
Mitochondrial OXPHOS generates most of the energy required for cellular function. biogenesis requires coordinated expression nuclear and mitochondrial genomes. This represents a unique challenge that highlights importance nuclear-mitochondrial genetic communication to Here we investigated transcriptomic functional consequences divergence in vitro vivo. We utilized xenomitochondrial cybrid cell lines containing DNA from common laboratory mouse Mus musculus domesticus (mtDNA) domesticus, or...
Abstract Microbiota modulate the immune system and recent studies suggest a functional relationship between microbiota, its metabolites CD8+ T cells, but whether this link is also relevant for cell memory unclear. We show that antigen-activated cells transferred into germ-free mice had transcriptional impairments in oxidative metabolism failed to transition with enhanced recall capacity. Conversely, microbiotaderived metabolite butyrate promoted potential secondary responses of activated...