Evidence map›Paper›PMID 42468529›Full record

ArticleImmunity2026

Purine and pyrimidine-based bacterial cyclic dinucleotides egress the phagosome and activate the innate immune sensor STING.

Stephanie A Ragland, Katherine E Lindblad, Yao Li, Joon H Choi, Daniel Okin, Joshua Q Mao, Desmond Richmond-Buccola, Daniela R Coronado, Madison R Brown, Scott B Snapper and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

12 authors.

Stephanie A RaglandDivision of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Katherine E LindbladDivision of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Yao LiDepartment of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Parker Institute of Cancer Immunotherapy at Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Joon H ChoiDivision of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Daniel OkinDivision of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Joshua Q MaoDivision of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Desmond Richmond-BuccolaDepartment of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Daniela R CoronadoDepartment of Immunology (Blavatnik Institute), Harvard Medical School, Boston, MA, USA.
Madison R BrownDivision of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Scott B SnapperDivision of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Boston MA O2115, USA.
Philip J KranzuschDepartment of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Jonathan C KaganDivision of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: jonathan.kagan@childrens.harvard.edu.

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
Research Training in Pulmonary Immunology and Allergy at MGHT32HL116275 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI David C Christiani, ANDREW D LUSTER · 2013 to 2026
$8.6M
Regulation of immunity by the cGAS-STING pathwayR01AI167993 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI JONATHAN C KAGAN · 2022 to 2026
$3.9M
Defining the pathways activated by Toll-like Receptors to stimulate immunityR37AI116550 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI JONATHAN C KAGAN · 2021 to 2026
$3.3M
Discovery of cGAS-like signaling enzymes in innate immunity and diseaseDP2GM146250 · NIGMS · DANA-FARBER CANCER INST · PI KRANZUSCH, PHILIP J · 2021 to 2024
$2.5M
Characterization of the myddosome, a protein complex that controls TLR signalingR01AI116550 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI KAGAN, JONATHAN C · 2017 to 2020
$1.8M
Regulation of innate immunity by the pathogen Staphylococcus aureusR01AI184490 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI JONATHAN C KAGAN · 2026 to 2026
$801k
The role of endogenous chimeric mRNA encoded GasderminD fusion proteins in immunityR01AI198293 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI JONATHAN C KAGAN · 2026 to 2026
$795k
Tetraacylated lipid A enhancement of checkpoint blocking cancer immunotherapyR21CA287104 · NCI · HARVARD MEDICAL SCHOOL · PI KASPER, DENNIS L. · 2024 to 2025
$436k
NCI NIH HHS R21 CA287104NHLBI NIH HHS T32 HL116275NIAID NIH HHS R01 AI116550NIAID NIH HHS R01 AI167993NIAID NIH HHS R01 AI184490NIAID NIH HHS R01 AI198293NIAID NIH HHS R37 AI116550NIDDK NIH HHS P30 DK034854NIGMS NIH HHS DP2 GM146250
6 · The paper itself

Abstract

Toll-like receptors (TLRs) are considered general sensors of bacterial encounters. Here, we examined whether other pattern recognition receptors are commonly activated during bacterial infection. TLR-independent interferon (IFN) responses were induced in macrophages in response to diverse bacterial encounters. Of the cytoplasmic receptor families examined, the cyclic dinucleotide (CDN) sensor STING was required for IFN responses to evolutionarily diverse bacteria. Various bacterial CDNs were present in murine tissues; these activated stimulator of interferon genes (STING) after bacteriolysis in phagolysosomes in a manner requiring two CDN transporters. Importantly, bacterial CDNs were increased in colonic biopsies from patients with inflammatory bowel disease. Systemic delivery of dead, CDN-laden bacteria promoted anti-tumor immunity in mice. Detection of diverse CDNs, including pyrimidine-based CDNs, was an evolutionarily conserved feature of STING, with distinct binding modes for purine- and pyrimidine-based CDNs. Thus, a phagocytosis-CDN-STING connection places cytoplasmic sensing as a common outcome of host-bacteria interactions that set the immune tone of a tissue, with implications for host defense.

Indexed as

BacteriaMembrane ProteinsNucleotides, CyclicPhagosomesPurinesPyrimidinesAnimalscGAS-STING Signaling PathwayHumansImmunity, InnateInnate Immunity RecognitionInterferonsMacrophagesMiceMice, Inbred C57BLMice, KnockoutInterferonsMembrane ProteinsNucleotides, CyclicPurinesPyrimidinesSTING1 protein, humanSting1 protein, mouseSTING Protein2′3′-cUMP-AMPbacteriacGAScyclic dinucleotidesinterferonLRRC8AmacrophagephagosomeSTINGtoll-like receptor

Identifiers

PMID42468529
PMCPMC13379678

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.