A5083735844- Immune Cell Function and Interaction
- Malaria Research and Control
- T-cell and B-cell Immunology
- Complement system in diseases
- Mosquito-borne diseases and control
- Immunotherapy and Immune Responses
- Single-cell and spatial transcriptomics
- HIV Research and Treatment
- CAR-T cell therapy research
- interferon and immune responses
- Invertebrate Immune Response Mechanisms
- Chemokine receptors and signaling
- Viral Infections and Vectors
- vaccines and immunoinformatics approaches
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Immune cells in cancer
- Aquaculture disease management and microbiota
- Cancer Immunotherapy and Biomarkers
- Lymphoma Diagnosis and Treatment
- Hematopoietic Stem Cell Transplantation
- Evolution and Genetic Dynamics
- Immune responses and vaccinations
Burnet Institute
2025
QIMR Berghofer Medical Research Institute
2016-2024
The University of Queensland
2017-2024
Translational Research Institute
2017-2019
Computational modeling defines T helper cell differentiation toward multiple fates during experimental malaria.
Parasite-specific antibodies protect against blood-stage Plasmodium infection. However, in malaria-endemic regions, it takes many months for naturally-exposed individuals to develop robust humoral immunity. Explanations this have focused on antigenic variation by Plasmodium, but considered less whether host production of parasite-specific antibody is sub-optimal. In particular, unclear immune factors might limit responses. Here, we explored the effect Type I Interferon signalling via IFNAR1...
Control of intracellular parasites responsible for malaria requires host IFN-γ+T-bet+CD4+ T cells (Th1 cells) with IL-10 produced by Th1 to mitigate the pathology induced this inflammatory response. However, these IL-10-producing (induced type I regulatory [Tr1]) can also promote parasite persistence or impair immunity reinfection vaccination. Here, we identified molecular and phenotypic signatures that distinguished IL-10-Th1 from IL-10+Tr1 in Plasmodium falciparum-infected people who...
Humoral immunity develops in the spleen during blood-stage Plasmodium infection. This elicits parasite-specific IgM and IgG, which control parasites protect against malaria. Studies mice have elucidated cells molecules driving humoral to Plasmodium, including CD4+ T cells, B interleukin (IL)-21 ICOS. IL-6, a cytokine readily detected Plasmodium-infected humans, is recognized other systems as driver of immunity. Here, we examined effect infection-induced IL-6 on Plasmodium. Using P. chabaudi...
Naive CD4+ T cells must differentiate in order to orchestrate immunity Plasmodium, yet understanding of their emerging phenotypes, clonality, spatial distributions, and cellular interactions remains incomplete. Here, we observe that splenic polyclonal toward helper 1 (Th1) follicular (Tfh)-like states exhibit rarer phenotypes not elicited among cell receptor (TCR) transgenic counterparts. TCR clones present at higher frequencies Th1 skewing, suggesting variation major histocompatibility...
T-follicular CD4 T (Tfh) cells play essential roles in antibody induction during infection and following vaccination. In humans, peripheral Tfh (pTfh) are commonly analysed based on expression of CXCR3 CCR6, with different subsets pTfh (pTfh1, pTfh2, pTfh17) associated a context-dependent manner. malaria, the specific development is not clear. Several studies human malaria vaccination have identified an important role pTfh2 cells, which associate while pTfh1 do not. However, vitro animal...
Inhibiting the host inflammatory response to malaria represents a potential strategy improve clinical outcomes and inhibit immunoregulatory pathways that underlie suboptimal development of antiparasitic immunity. Ruxolitinib is JAK 1/2 inhibitor reduces biomarkers when used in myeloproliferative disorders, inhibits type-1 interferons enhances CD4+ T cell immunity combined with anti-parasitic drugs animal models. Here we report results double-blind randomised placebo-controlled trial...
Abstract We describe an MHC class II (I-Ab)–restricted TCR transgenic mouse line that produces CD4+ T cells specific for Plasmodium species. This line, termed PbT-II, was derived from a cell hybridoma generated to blood-stage berghei ANKA (PbA). PbT-II responded all species and stages tested so far, including rodent (PbA, P. NK65, chabaudi AS, yoelii 17XNL) human (Plasmodium falciparum) parasites as well irradiated PbA sporozoites. can provide help generation of Ab infection control this...
Abstract Plasmodium falciparum malaria drives immunoregulatory responses across multiple cell subsets, which protects from immunopathogenesis, but also hampers the development of effective anti-parasitic immunity. Understanding induced tolerogenic in specific subsets may inform strategies to boost protective immunity during drug treatment and vaccination. Here, we analyse immune landscape with single RNA sequencing P. malaria. We identify type sub-clustered major types. Malaria is associated...
Abstract Differentiation of CD4+ Th cells is critical for immunity to malaria. Several innate immune signaling pathways have been implicated in the detection blood-stage Plasmodium parasites, yet their influence over cell remains unclear. In this study, we used Plasmodium-reactive TCR transgenic T cells, termed PbTII during nonlethal P. chabaudi AS and yoelii 17XNL infection mice, examine development vivo. We found no role caspase1/11, stimulator IFN genes, or mitochondrial...
Severe malaria and associated high parasite burdens occur more frequently in humans lacking robust adaptive immunity to Plasmodium falciparum Nevertheless, the host may partly control blood-stage numbers while is gradually established. Parasite has typically been attributed enhanced removal of parasites by host, although vivo quantification this phenomenon remains challenging. We used a unique approach determine fate single cohort semisynchronous, berghei ANKA- or yoelii 17XNL-parasitized...
Plasmodium parasites invade and multiply inside red blood cells (RBC). Through a cycle of maturation, asexual replication, rupture release multiple infective merozoites, parasitised RBC (pRBC) can reach very high numbers in vivo, process that correlates with disease severity humans experimental animals. Thus, controlling pRBC prevent or ameliorate malaria. In endemic regions, circulating parasite-specific antibodies associate immunity to parasitemia. Although vitro assays reveal protective...
Abstract Combinations of mAbs that target various components T-cell activation/inhibition may work synergistically to improve antitumor immunity against cancer. In this study, we investigated the therapeutic potential combining an anticancer vaccination strategy with antibodies targeting immune stimulatory (4-1BB) and inhibitory (PD-1) receptor, in a preclinical model spontaneously arising c-Myc–driven B-cell lymphoma. Eμ-myc transgenic mice, reveal 4-1BB agonistic mAb treatment alone was...
Monocytosis is considered a poor prognostic factor for many cancers, including B cell lymphomas. The mechanisms by which different monocyte subsets support the growth of lymphoma poorly understood. Using pre-clinical mouse model non-Hodgkin's (B-NHL), we investigated impact tumor progression on circulating levels, subset distribution and their activity, with focus immune suppression. B-NHL development corresponded significant expansion initially classical (Ly6Chi) non-classical (Ly6Clo)...
Immunomodulatory therapies can effectively control haematological malignancies. Previously we reported the effectiveness of combination immunotherapies that centre on 4-1BB-targeted co-stimulation CD8 + T cells, particularly when simultaneously harnessing immune adjuvant properties Natural Killer (NKT) cells. The objective this study was to assess agonistic anti-4-1BB antibody-based therapy against two aggressive forms acute myeloid leukemia (AML).Anti-4-1BB treatment alone resulted in...
Acute gastrointestinal (GI) graft-versus-host disease (GVHD) is a primary determinant of mortality after allogeneic hematopoietic stem cell transplantation (alloSCT). The condition mediated by alloreactive donor CD4+ T cells that differentiate into pathogenic subsets expressing IFN-γ, IL-17A, or GM-CSF and regulated IL-10 and/or Foxp3. Developmental relationships between Th states during priming in mesenteric lymph nodes (mLNs) effector function the GI tract remain undefined at genome scale....
Abstract Children in malaria-endemic regions can experience repeated Plasmodium infections over short periods of time. Effects re-infection on multiple co-existing CD4 + T cell subsets remain unresolved. Here, we examine antigen-experienced cells during mice, using scRNA-seq/TCR-seq and spatial transcriptomics. TCR transgenic EM initiate rapid Th1/Tr1 recall responses prior to proliferating, while GC Tfh counterparts are refractory, with CM /Tfh-like exhibiting modest non-proliferative...