Clustering of Activated CD8 T Cells Around Malaria-Infected Hepatocytes Is Rapid and Is Driven by Antigen-Specific Cells

Malaria, a disease caused by parasites of the Plasmodium genus, begins when Plasmodium-infected mosquitoes inject malaria sporozoites while searching for blood. Sporozoites migrate from the skin via blood to the liver, infect hepatocytes, and form liver stages which in mice 48 h later escape into blood and cause clinical malaria. Vaccine-induced activated or memory CD8 T cells are capable of locating and eliminating all liver stages in 48 h, thus preventing the blood-stage disease. However, the rules of how CD8 T cells are able to locate all liver stages within a relatively short time period remains poorly understood. We recently reported formation of clusters consisting of variable numbers of activated CD8 T cells around Plasmodium yoelii (Py)-infected hepatocytes. Using a combination of experimental data and mathematical models we now provide additional insights into mechanisms of formation of these clusters. First, we show that a model in which cluster formation is driven exclusively by T-cell-extrinsic factors, such as variability in “attractiveness” of different liver stages, cannot explain distribution of cluster sizes in different experimental conditions. In contrast, the model in which cluster formation is driven by the positive feedback loop (i.e., larger clusters attract more CD8 T cells) can accurately explain the available data. Second, while both Py-specific CD8 T cells and T cells of irrelevant specificity (non-specific CD8 T cells) are attracted to ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Malaria parasites undergo several stages in their complex lifecycle. To achieve reductions in both the individual disease burden and malaria transmission within communities, a multi-stage malaria vaccine with high effectiveness and durability is a more efficacious strategy compared with a single-stage vaccine. Here, we generated viral-vectored vaccines based on human adenovirus type 5 (AdHu5) and adeno-associated virus serotype 1 (AAV1) expressing a fusion protein of the pre-erythrocytic stage Plasmodium falciparum circumsporozoite protein (PfCSP) and the transmission-blocking sexual stage P25 protein (Pfs25). A two-dose h...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Funding Opportunity RFA-AI-19-059 from the NIH Guide for Grants and Contracts. The purpose of this initiative is to stimulate basic research, discovery, and early translational research to enable and accelerate the generation of highly efficacious pre-erythrocytic stage, sporozoite-based vaccines. Cross-fertilization and collaboration among investigators from malaria vaccine research and other basic research areas such as parasite biology, parasite genomics, pathogenesis, and host immunology are highly encouraged. The goal is to generate one or more promising vaccine candidates against human malaria that exhibit performan...
Source: NIH Funding Opportunities (Notices, PA, RFA) - Category: Research Source Type: funding
Bill Gates told an audience at the University of Cambridge on Monday that global malnutrition will be solved and malaria will be virtually eliminated by 2040 if world leaders choose to fund scientific innovation. Speaking at the Cambridge Union in England, the Microsoft co-founder said: “I’m lucky that my work gives me a view of all the amazing discoveries in the works right now. That’s why I’m able to predict the future.” Gates was named the 2019 recipient of the Professor Hawking Fellowship, founded by the Cambridge Union Society in 2017 in honor of Stephen Hawking’s contribution to t...
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized global health Source Type: news
In this study, the level of polymorphisms, haplotypes and natural selection of full-length pkmsp8 in 37 clinical samples from Malaysian Borneo along with 6 lab-adapted strains were investigated. Low levels of polymorphism were observed across the full-length gene, the double epidermal growth factor (EGF) domains were mostly conserved, and non-synonymous substitutions were absent. Evidence of strong negative selection pressure in the non-EGF regions were found indicating functional constrains acting at different domains. Phylogenetic haplotype network analysis identified shared haplotypes and indicated geographical clusteri...
Source: Korean Journal of Parasitology - Category: Parasitology Tags: Korean J Parasitol Source Type: research
It may be possible to eradicate malaria—one of history’s deadliest diseases—from the planet by 2050, according to a coalition of 41 leading scientists, economists and health-policy experts writing in the Lancet. “Malaria is one of the oldest and deadliest diseases of humankind,” says Sir Richard Feachem, one of the report’s authors and co-chair of the Lancet commission on malaria eradication. “If we, humankind, were to take on this challenge and eradicate malaria by 2050, it would be an achievement of historic proportions. There would be nothing quite like it.” Malaria, a mos...
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized Infectious Disease onetime Source Type: news
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Source: Proteomics - Category: Biochemistry Authors: Tags: Research Article Source Type: research
Three-year review says new vaccines for eradicating disease are only 40% effectiveMalaria will not be eradicated in the foreseeable future even though it is achievable and would save millions of lives, according to World Health Organization (WHO) experts following a three-year review.The WHO remains committed to the “disappearance of every single malaria parasite from the face of the planet”, as it has been since the UN organisation was launched in 1948, said Dr Pedro Alonso, the director of its global malaria programme.Continue reading...
Source: Guardian Unlimited Science - Category: Science Authors: Tags: World Health Organization Malaria World news Society Science Medicine Medical research Global development Source Type: news
Induction of memory CD8+ T cells is important for controlling infections such as malaria and HIV/AIDS and for cancer immunotherapy. Accurate assessment of antigen-specific (Ag-specific) CD8+ T cells is critical for vaccine optimization and for defining correlates of protection. However, conditions for determining Ag-specific CD8+ T cell responses ex vivo using intracellular cytokine staining (ICS) may be variable, especially in humans with complex antigens. Here, we used an attenuated whole parasite malaria vaccine model in humans and various experimental infections in mice to show that the duration of antigenic stimulatio...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
NICE proposes use of antiseptic creams instead Related items fromOnMedica Single-dose malaria drug eliminates parasite from liver Patients often avoid vaccinations due to fear of side effects Double check patients with ‘penicillin’ allergy to avoid MRSA risk Ibuprofen not a safe alternative to antibiotics for uncomplicated UTIs Inhaled corticosteroids linked to higher infection risk
Source: OnMedica Latest News - Category: UK Health Source Type: news
ms TE Abstract SUMMARYProtozoan Plasmodium parasites are the causative agents of malaria, a deadly disease that continues to afflict hundreds of millions of people every year. Infections with malaria parasites can be asymptomatic, with mild or severe symptoms, or fatal, depending on many factors such as parasite virulence and host immune status. Malaria can be treated with various drugs, with artemisinin-based combination therapies (ACTs) being the first-line choice. Recent advances in genetics and genomics of malaria parasites have contributed greatly to our understanding of parasite population dynamics, transmis...
Source: Clinical Microbiology Reviews - Category: Microbiology Authors: Tags: Clin Microbiol Rev Source Type: research
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