- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Influenza Virus Research Studies
- Immune Response and Inflammation
- Chemokine receptors and signaling
- Immune responses and vaccinations
- Respiratory viral infections research
- Neonatal Respiratory Health Research
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Cytokine Signaling Pathways and Interactions
- Viral gastroenteritis research and epidemiology
- Lung Cancer Treatments and Mutations
- Bacterial Infections and Vaccines
- Ubiquitin and proteasome pathways
- Respiratory Support and Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Tryptophan and brain disorders
- Parasites and Host Interactions
- Effects of Radiation Exposure
- Animal Disease Management and Epidemiology
- Reproductive System and Pregnancy
- vaccines and immunoinformatics approaches
- Systemic Lupus Erythematosus Research
University of Glasgow
2014-2024
Centre for Immunity, Infection and Evolution
2006-2023
Howard Hughes Medical Institute
2006-2014
National Jewish Health
2006-2014
University of Colorado Denver
2006-2014
University of Colorado Health
2006-2008
University of Edinburgh
1962-2007
Zero to Three
2007
Molina Center for Energy and the Environment
2006
Augusta University
2002
Summary Cells expressing indoleamine 2,3‐dioxygenase (IDO), an enzyme which catabolizes tryptophan, prevent T‐cell proliferation in vitro , suppress maternal antifetal immunity during pregnancy and inhibit T‐cell‐mediated responses to tumour‐associated antigens. To examine the mechanistic basis of these phenomena we activated naïve murine T cells chemically defined tryptophan‐free media. Under conditions expressed CD25 CD69 progressed through first 12 hr G0/G1 phase but did not express CD71,...
To understand more about how the body recognizes alum we characterized early innate and adaptive responses in mice injected with adjuvant. Within hours of exposure, induces a type 2 response by an influx eosinophils, monocytes, neutrophils, DCs, NK cells NKT cells. In addition, at least 13 cytokines chemokines are produced within 4 h injection including IL-1beta IL-5. Optimal production some these, IL-1beta, depends upon both macrophages mast cells, whereas others, such as IL-5, on only,...
B cells are well documented as APC; however, their role in supporting and programming the T cell response vivo is still unclear. Studies using cell-deficient mice have given rise to contradictory results. We used mixed BM chimeric define contribution that make APC. When compartment deficient MHC class II, while other APC largely normal, clonal expansion significantly reduced differentiation of into cytokine-secreting effector impaired (in particular, Th2 cells). The development memory...
CD4 T cell help for B cells is critical effective Ab responses. Although many of the molecules involved in helper functions naive have been characterized, much less known about capabilities memory cells, an important consideration design vaccines that aim to prime protective cells. In this study, we demonstrate enable expand more rapidly and class switch earlier than do primary responding This accelerated response does not require large numbers similar provide However, only express follicle...
Vaccines can greatly reduce the spread of and deaths from many infectious diseases. However, infections have no successful vaccines. Better understanding generation protective CD8 memory T cells by vaccination is essential for rational design new vaccines that aim to prime cellular immune responses. Here we demonstrate combination two adjuvants are currently licensed use in humans be used long-lived protect mice viral challenge. The universally adjuvant, aluminum salts, primed cells;...
Highlights•Mice deficient in CCR1, CCR2, CCR3, and CCR5 (iCCRs) develop normally•iCCRs redundantly establish resting tissue-resident myelomonocytic cell populations•CCR2 dominates controlling monocyte recruitment acute inflammation•iCCRs are not involved neutrophil or lymphocyte inflammationSummaryCurrently, we lack an understanding of the individual combinatorial roles for chemokine receptors inflammatory process. We report studies on mice with a compound deletion Ccr1, Ccr2, Ccr3, Ccr5,...
The production of high affinity, class switched antibodies produced by B cells hinges on the effective differentiation T follicular helper (Tfh) cells. Here we define conditions specifically enhancing Tfh and providing protection in a model influenza infection. responses were associated with prolonged antigen presentation dendritic (DCs), which maintained cell/DC interactions into stage 3 (>72 hr) activation. Blocking ablated generation, demonstrating causal link between cell-DC behaviour...
Periodontitis (PD) results from complex interactions between a dysbiotic oral microbiota and dysregulated host immune response. The inflammatory infiltrate in the gingiva of PD patients includes an abundance B cells, implicating these cells immunopathology. We sought to investigate role using murine model. Wild-type or B-cell-deficient (μMT) mice were orally infected with Porphyromonas gingivalis. One six weeks following infection, lymphocyte populations cervical draining lymph nodes (dLN)...
Immunological memory is a hallmark of adaptive immunity, and understanding T cell will be central to the development effective cell-mediated vaccines. The characteristics functions CD4 cells have not been well defined. Here we demonstrate that increased size secondary response solely consequence antigen-specific precursor frequency within pool. Memory proliferated less than primary responding cells, even same host. By analyzing entry into cycle, found two populations similarly until day 5;...
Chemokines have been shown to be essential players in a range of cancer contexts. In this study, we demonstrate that mice deficient the atypical chemokine receptor Ackr2 display impaired development metastasis vivo both cell line and spontaneous models. Further analysis reveals relates increased expression CCR2, specifically by KLRG1
RNA viruses are a major human health threat. The life cycles of many highly pathogenic like influenza A virus (IAV) and Lassa depends on host mRNA, because viral polymerases cleave 5′-m7G-capped transcripts to prime mRNA synthesis ("cap-snatching"). We hypothesized that start codons within cap-snatched could generate chimeric human-viral mRNAs with coding potential. report the existence this mechanism gene origination, which we named "start-snatching." Depending reading frame,...
Abstract We have addressed the role of inducible costimulator (ICOS) in development T cell help for B cells and generation, survival reactivation memory CD4 cells. find that while all antibody isotypes (including IgG2c) is impaired ICOS knockout (ICOS‐KO) mice, IFN‐γ response little affected, indicating a defect helper function unrelated to cytokine production. In addition, ICOS‐negative do not accumulate follicles. Secondary (memory), but primary, clonal proliferation antigen‐specific...
T cell protective immunity is associated with multifunctional memory cells that produce several different cytokines. Currently, our understanding of when and how these are generated limited. We have used an influenza virus mouse infection model to investigate whether the cytokine profile reflective primary responding or skewed toward a distinct profile. found that, in comparison cells, tended make multiple cytokines simultaneously. Analysis timings release by virus-specific demonstrated CD4...
Inflammatory chemokine receptors CCR1/2/3/5 (iCCRs) play an important role in the recruitment of immune cells involved innate functions and orchestrating adaptive response. Here we utilise influenza A virus (IAV) challenge to investigate combinatorial roles iCCRs anti-IAV We did not observe any gross differences infection-driven pathology absence iCCRs. Despite iCCR deletion resulting decreased migration monocytes, migratory macrophages B lungs during acute IAV infection, no dendritic cell...
As for most things in life, turning off the immune system is as important them on. Biologists usually like to focus on positive, ways which natural processes get started. However, this not case system. Numerous studies have addressed problems of resolving responses, perhaps because inhibition and resolution response are so important, required, they are, prevent autoimmunity reduce ongoing inflammation. The body responds infection by inducing many processes. Often granulocytes first cells...