A5013679753- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- IL-33, ST2, and ILC Pathways
- FOXO transcription factor regulation
- Immune cells in cancer
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Research on Leishmaniasis Studies
- Cytomegalovirus and herpesvirus research
- Chronic Lymphocytic Leukemia Research
- interferon and immune responses
- Cancer Immunotherapy and Biomarkers
- Immune responses and vaccinations
- Lymphoma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Insect symbiosis and bacterial influences
- MicroRNA in disease regulation
- Blood Coagulation and Thrombosis Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Trypanosoma species research and implications
- Viral Infections and Vectors
- Immune Response and Inflammation
- Cancer Research and Treatments
- Peptidase Inhibition and Analysis
Peter Doherty Institute
2019-2025
The University of Melbourne
2019-2025
University of California, San Diego
2016-2019
University of Lausanne
2012-2017
Swiss Vaccine Research Institute
2012-2017
Technical University of Munich
2010-2014
University Hospital of Lausanne
2012
CD8+ T cells that respond to chronic viral infections or cancer are characterized by the expression of inhibitory receptors such as programmed cell death protein 1 (PD-1) and impaired production cytokines. This state restrained functionality-which is referred exhaustion1,2-is maintained precursors exhausted (TPEX) express transcription factor (TCF1), self-renew give rise TCF1- effector cells3-6. Here we show long-term proliferative potential, multipotency repopulation capacity during...
Chronic infections induce T cells showing impaired cytokine secretion and up-regulated expression of inhibitory receptors such as PD-1. What determines the acquisition this chronic phenotype how it impacts cell function remain vaguely understood. Using newly generated recombinant antigen variant-expressing lymphocytic choriomeningitis virus (LCMV) strains, we uncovered that differentiation a or exhausted depend critically on frequency receptor (TCR) engagement less significantly strength TCR...
The presence of the endogenous Leishmania RNA virus 1 (LRV1) replicating stably within some parasite species has been associated with development more severe forms leishmaniasis and relapses after drug treatment in humans. Here, we show that disease-exacerbatory role LRV1 relies on type I IFN (type IFNs) production by macrophages signaling vivo. Moreover, infecting mice LRV1-cured guyanensis (LgyLRV1- ) strain parasites followed increased lesion size burden, quantitatively reproducing...
T cell factor 1 (Tcf-1) expressing CD8+ cells exhibit stem-like self-renewing capacity, rendering them key for immune defense against chronic viral infection and cancer. Yet, the signals that promote formation maintenance of these (CD8+SL) remain poorly defined.Studying differentiation in mice with infection, we identified alarmin interleukin-33 (IL-33) as pivotal expansion functioning CD8+SL well virus control. IL-33 receptor (ST2)-deficient exhibited biased end premature loss Tcf-1....
T follicular helper (T
Immunity following an acutely resolved infection or the long-term equipoise of chronic viral infections often depends on maintenance antigen-specific CD8+ T cells, yet ongoing transcriptional requirements these cells remain unclear. We show that active and continuous programming by FOXO1 is required for functional a memory population. Upon Foxo1 deletion resolution infection, rapidly lost their characteristic gene expression, gradually declined in number, were impaired self-renewal. This was...
Upon infection with an intracellular pathogen, cytotoxic CD8+ T cells develop diverse differentiation states characterized by function, localization, longevity, and the capacity for self-renewal. The program of is determined, in part, FOXO1, a transcription factor known to integrate extrinsic input order specify survival, DNA repair, self-renewal, proliferation. At issue whether state cell specified initial conditions activation or actively maintained. To study spectrum differentiation, we...
Abstract Chronic stimulation of CD8 + T cells triggers exhaustion, a distinct differentiation state with diminished effector function. Exhausted exist in multiple states, from stem-like progenitors that are the key mediators response to checkpoint blockade, through terminally exhausted cells. Due its clinical relevance, there is substantial interest defining pathways control and maintenance these subsets. Here, we show chronic antigen induces anergy-associated transcription factor EGR2...
Abstract NLRC5 is a transcriptional regulator of MHC class I (MHCI), which maintains high MHCI expression particularly in T cells. Recent evidence highlights an important NK–T-cell crosstalk, raising the question on whether specifically modulates this interaction. Here we show that NK cells from Nlrc5 -deficient mice exhibit moderate alterations inhibitory receptor and responsiveness. Interestingly, required to protect them NK-cell-mediated elimination upon inflammation. Using...
Stem-like T cells are attractive immunotherapeutic targets in patients with cancer given their ability to proliferate and differentiate into effector progeny. Thus, identifying enhanced stemness understanding developmental requirements of broad clinical therapeutic interest. Here, we demonstrate that during acute infection, the transcriptional regulator inhibitor DNA binding 3 (ID3) identifies stem-like uniquely adapted generate precursors exhausted (Tpex) response chronic infection or...
Abstract Human kallikrein-related peptidases (KLKs) are 15 homologous serine proteases involved in several (patho)physiological processes, including cancer. Secreted as precursors, they activated upon proteolytic release of a short pro-peptide. We searched for interconnection KLKs within extracellular networks leading to activation protease zymogens and found that (i) pro-KLK by other is scarce, with the exception pro-KLK11, which efficiently KLK4 5; (ii) pro-KLK4 matrix metalloproteinase 3;...
Recent studies have shown that a cytoplasmic virus called Leishmaniavirus (LRV) is present in some Leishmania species and acts as potent innate immunogen, aggravating lesional inflammation development mice. In humans, the presence of LRV guyanensis L. braziliensis was significantly correlated with poor treatment response symptomatic relapse. So far, no clinical effort has used for prophylactic purposes. this context, we designed an original vaccine strategy targeted nested parasites to...