Evidence map›Paper›PMID 40338743›Full record

ArticleCell reports2025

Phagosomal RNA sensing through TLR8 controls susceptibility to tuberculosis.

Charlotte Maserumule, Charlotte Passemar, Olivia S H Oh, Kriztina Hegyi, Karen Brown, Aaron Weimann, Adam Dinan, Sonia Davila, Catherine Klapholz, Josephine Bryant and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors.

Charlotte MaserumuleMolecular Immunity Unit, University of Cambridge Department of Medicine, MRC-Laboratory of Molecular Biology, Cambridge, UK.
Charlotte PassemarMolecular Immunity Unit, University of Cambridge Department of Medicine, MRC-Laboratory of Molecular Biology, Cambridge, UK; Victor Philip Dahdaleh Heart & Lung Research Institute, University of Cambridge, Cambridge, UK.
Olivia S H OhDepartment of Microbiology, The Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Kriztina HegyiMolecular Immunity Unit, University of Cambridge Department of Medicine, MRC-Laboratory of Molecular Biology, Cambridge, UK.
Karen BrownMolecular Immunity Unit, University of Cambridge Department of Medicine, MRC-Laboratory of Molecular Biology, Cambridge, UK; Victor Philip Dahdaleh Heart & Lung Research Institute, University of Cambridge, Cambridge, UK; Cambridge Centre for Lung Infection, Royal Papworth Hospital, Cambridge, UK.
Aaron WeimannMolecular Immunity Unit, University of Cambridge Department of Medicine, MRC-Laboratory of Molecular Biology, Cambridge, UK; Victor Philip Dahdaleh Heart & Lung Research Institute, University of Cambridge, Cambridge, UK; Cambridge Centre for AI in Medicine, University of Cambridge, Cambridge, UK.
Adam DinanMolecular Immunity Unit, University of Cambridge Department of Medicine, MRC-Laboratory of Molecular Biology, Cambridge, UK; Victor Philip Dahdaleh Heart & Lung Research Institute, University of Cambridge, Cambridge, UK; Cambridge Centre for AI in Medicine, University of Cambridge, Cambridge, UK.
Sonia DavilaInfectious Disease Group, Genome Institute of Singapore, Singapore, Singapore; SingHealth Duke-NUS Institute of Precision Medicine, SingHealth Duke-NUS Genomic, Medicine Centre, Cardiovascular and Metabolic Disorder Program, Duke-NUS Medical, School, Singapore, Singapore.
Catherine KlapholzMolecular Immunity Unit, University of Cambridge Department of Medicine, MRC-Laboratory of Molecular Biology, Cambridge, UK.
Josephine BryantMolecular Immunity Unit, University of Cambridge Department of Medicine, MRC-Laboratory of Molecular Biology, Cambridge, UK; Cambridge Centre for AI in Medicine, University of Cambridge, Cambridge, UK.
Deepshikha VermaMycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA.
Jacob GadwaMycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA.
Shivankari KrishnananthasivamDepartment of Microbiology, The Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Kridakorn VongtongsaleeMycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA.
Edward KendallMycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA.
Andres TrellesMycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA.
Martin L HibberdInfectious Disease Group, Genome Institute of Singapore, Singapore, Singapore; London School of Hygiene and Tropical Medicine, London, UK.
Joaquín SanzInstitute for Bio-computation and Physics of Complex Systems BIFI, Department of Theoretical Physics, University of Zaragoza, Zaragoza, Spain.
Jorge BertolInstitute for Bio-computation and Physics of Complex Systems BIFI, Department of Theoretical Physics, University of Zaragoza, Zaragoza, Spain.
Lucia Vázquez-IniestaDepartment of Preventive Medicine, Public Health and Microbiology, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
Kaliappan AndiICMR-National Institute for Research in Tuberculosis, Chennai, India.
S Siva KumarICMR-National Institute for Research in Tuberculosis, Chennai, India.
Diane OrdwayMycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA.
Rafael Prados-RosalesDepartment of Preventive Medicine, Public Health and Microbiology, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
Paul A MacAryDepartment of Microbiology, The Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Electronic address: micpam@nus.edu.sg.
R Andres FlotoMolecular Immunity Unit, University of Cambridge Department of Medicine, MRC-Laboratory of Molecular Biology, Cambridge, UK; Victor Philip Dahdaleh Heart & Lung Research Institute, University of Cambridge, Cambridge, UK; Cambridge Centre for Lung Infection, Royal Papworth Hospital, Cambridge, UK; Cambridge Centre for AI in Medicine, University of Cambridge, Cambridge, UK. Electronic address: arf27@cam.ac.uk.

Funding

Role of mycobacterial dynamin-like proteins in the biogenesis of membrane vesicles, and host-pathogen interactionsR01AI162821 · NIAID · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI RODRIGUEZ, GLORIA MARCELA, SALGAME, PADMINI · 2021 to 2025
$3.4M
NIAID NIH HHS R01 AI162821Wellcome Trust 107032Wellcome Trust 226602
6 · The paper itself

Abstract

Genetic determinants of susceptibility to Mycobacterium tuberculosis (Mtb) remain poorly understood but could provide insights into critical pathways involved in infection, informing host-directed therapies and enabling risk stratification at individual and population levels. Through a genome-wide forward genetic screen, we identify Toll-like receptor 8 (TLR8) as a key regulator of intracellular killing of Mtb. Pharmacological TLR8 activation enhances the killing of phylogenetically diverse clinical isolates of drug-susceptible and multidrug-resistant Mtb by macrophages and during in vivo infection in mice. TLR8 is activated by phagosomal mycobacterial RNA released by extracellular membrane vesicles and enhances xenophagy-dependent Mtb killing. We find that the TLR8 variant M1V, common in Far Eastern populations, enhances intracellular killing of Mtb through preferential signal-dependent trafficking to phagosomes. TLR8 signaling may, therefore, both regulate susceptibility to tuberculosis and provide novel drug targets.

Indexed as

Mycobacterium tuberculosisPhagosomesRNA, BacterialToll-Like Receptor 8TuberculosisAnimalsGenetic Predisposition to DiseaseHumansMacrophagesMiceMice, Inbred C57BLSignal TransductionRNA, BacterialTLR8 protein, humanToll-Like Receptor 8CP: ImmunologyCRISPRdrug discoveryinfectionmacrophagesmycobacteriaphagosomeresiquimodTLR8tuberculosisxenophagy

Identifiers

PMID40338743
PMCPMC7618372

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.