The innate immune recognition of the malaria-causing pathogen Plasmodium falciparum (P. falciparum) is not fully explored. Here, we identify the nucleoside 5'-methylthioinosine (MTI), a Plasmodium-specific intermediate of the purine salvage pathway, as a pathogen-derived Toll-like receptor 8 (TLR8) agonist. Co-incubation of MTI with the TLR8 enhancer poly(dT) as well as synthetic or P. falciparum-derived RNA strongly increase its stimulatory activity. Of note, MTI generated from methylthioadenosine (MTA) by P. falciparum lysates activates TLR8 when MTI metabolism is inhibited by immucillin targeting the purine nucleoside phosphorylase (PfPNP). Importantly, P. falciparum-infected red blood cells incubated with MTI or cultivated with MTA and immucillin lead to TLR8-dependent interleukin-6 (IL-6) production in human monocytes. Our data demonstrate that the nucleoside MTI is a natural human TLR8 ligand with possible in vivo relevance for innate sensing of P. falciparum.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.celrep.2022.110691 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Bacterial purine metabolism modulates C. elegans development and stress tolerance via DAF-16.
FEBS J
December 2024
Department of Chemical Engineering, Texas A&M University, College Station, TX, USA.
The purine metabolism is crucial for cellular function and is a conserved metabolic network from prokaryotes to humans. While extensively studied in microorganisms like yeast and bacteria, the impact of perturbing dietary intermediates from the purine biosynthesis on animal development and growth remains poorly understood. We utilized Caenorhabditis elegans as the metazoan model to investigate the mechanisms underlying this deficiency.
View Article and Find Full Text PDFPolyphosphate Kinase from , One Enzyme Catalyzing a Two-Step Cascade Reaction to Synthesize ATP from AMP.
Int J Mol Sci
December 2024
Department of Bio-Organic Chemistry, Instituto de Química Orgánica General, CSIC (IQOG-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
This study characterizes a novel polyphosphate kinase from (PPK2-III), an enzyme with potential applications in ATP regeneration processes. Bioinformatic and structural analyses confirmed the presence of conserved motifs characteristic of PPK2 enzymes, including Walker A and B motifs, and the subclass-specific residue E137. Molecular docking simulations showed AMP had the highest binding affinity (-7.
View Article and Find Full Text PDFJianghua Kucha black tea containing theacrine attenuates depression-like behavior in CUMS mice by regulating gut microbiota-brain neurochemicals and cytokines.
Food Res Int
December 2024
Tea Research Institute, Hunan Academy of Agricultural Sciences, Changsha, Hunan 410125, China; Longping Branch, College of Biology, Hunan University, Changsha, Hunan 410125, China. Electronic address:
Theacrine and theaflavins are known for their potential to mitigate depression and cognitive impairment. Jianghua Kucha black tea (JH) contains both compounds, yet its antidepressant properties are seldom documented. This study evaluated the effects of JH on depression in chronic unpredictable mild stress (CUMS) mice and explored the underlying mechanisms through integrative analyses of gut microbiota and fecal metabolomics.
View Article and Find Full Text PDFTandem Imaging of Breath Ethanol and Acetaldehyde Based on Multiwavelength Enzymatic Biofluorometry.
ACS Sens
December 2024
Department of Biomedical Devices and Instrumentation, Laboratory for Biomaterials and Bioengineering, Institute of Integrated Research, Institute of Science Tokyo, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
Highly sensitive and selective imaging of human-borne volatile organic compounds (VOCs) enables an intuitive understanding of their concentrations and release sites. While multi-VOC imaging methods have the potential to facilitate step-by-step metabolic tracking and improve disease screening accuracy, no such system currently exists. In this study, we achieved simultaneous imaging of ethanol (EtOH) and acetaldehyde (AcH), the starting molecule and an intermediate metabolite of alcohol metabolism, using a multiwavelength VOC imaging system.
View Article and Find Full Text PDFStructural basis of deoxynucleotide addition by HIV-1 RT during reverse transcription.
Nat Commun
December 2024
Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Reverse transcription of the retroviral RNA genome into DNA is an integral step during HIV-1 replication. Despite a wealth of structural information on reverse transcriptase (RT), we lack insight into the intermediate states of DNA synthesis. Using catalytically active substrates, and a blot/diffusion cryo-electron microscopy approach, we capture 11 structures encompassing reactant, intermediate and product states of dATP addition by RT at 2.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!