Evidence mapPaperPMID 40947770Full record

ArticleAnimal models and experimental medicine2025

Molecular dynamics of the host response to Streptococcus pneumoniae pneumonia in baboons.

Bryan D Kraft, Ashlee M Valente, Ephraim L Tsalik, Micah T McClain, Marshall Nichols, Thomas W Burke, Ricardo Henao, Erik J Soderblom, J Will Thompson, M Arthur Moseley and 9 more

Abstract read
In one paragraph

Article in Animal models and experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

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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

2 citing papers in PubMed.

  1. Immune dysregulation inFrontiers in immunology · 2026
    Review
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4 · The record

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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

19 authors.

Bryan D KraftDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.ORCID 0000-0001-6545-8803
Ashlee M ValenteCenter for Infectious Disease Diagnostics and Innovation, Duke University School of Medicine, Durham, North Carolina, USA.
Ephraim L TsalikDurham Veterans Affairs Health Care System, Durham, North Carolina, USA.
Micah T McClainDurham Veterans Affairs Health Care System, Durham, North Carolina, USA.
Marshall NicholsCenter for Infectious Disease Diagnostics and Innovation, Duke University School of Medicine, Durham, North Carolina, USA.
Thomas W BurkeCenter for Infectious Disease Diagnostics and Innovation, Duke University School of Medicine, Durham, North Carolina, USA.
Ricardo HenaoCenter for Infectious Disease Diagnostics and Innovation, Duke University School of Medicine, Durham, North Carolina, USA.
Erik J SoderblomProteomics and Metabolomics Shared Resource, Duke University School of Medicine, Durham, North Carolina, USA.
J Will ThompsonProteomics and Metabolomics Shared Resource, Duke University School of Medicine, Durham, North Carolina, USA.
M Arthur MoseleyProteomics and Metabolomics Shared Resource, Duke University School of Medicine, Durham, North Carolina, USA.
Lori L HudsonCenter for Infectious Disease Diagnostics and Innovation, Duke University School of Medicine, Durham, North Carolina, USA.
Timothy VeldmanCenter for Infectious Disease Diagnostics and Innovation, Duke University School of Medicine, Durham, North Carolina, USA.
Olga M BetterCenter for Infectious Disease Diagnostics and Innovation, Duke University School of Medicine, Durham, North Carolina, USA.
Mert AydinCenter for Infectious Disease Diagnostics and Innovation, Duke University School of Medicine, Durham, North Carolina, USA.
Anna MazurCenter for Infectious Disease Diagnostics and Innovation, Duke University School of Medicine, Durham, North Carolina, USA.
Karen E Welty-WolfDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Claude A PiantadosiDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Geoffrey S GinsburgAll of Us Research Program, National Institutes of Health, Bethesda, Maryland, USA.
Christopher W WoodsDurham Veterans Affairs Health Care System, Durham, North Carolina, USA.

Funding

Bill and Melinda Gates Foundation OPP1017554
6 · The paper itself

Abstract

backgroundBacterial pneumonia remains a leading cause of morbidity and mortality worldwide despite the widespread availability of antibiotics. Novel pneumonia therapies and biomarkers are urgently needed to improve outcomes and advance personalized therapy. Using an established baboon model of S. pneumoniae pneumonia, we sought to characterize the temporal dynamics of pneumonia host responses to identify novel potential diagnostic and therapeutic molecular targets.

methodsWe performed whole blood transcriptomics, unbiased proteomics, and peripheral cytokine measurements serially in baboons inoculated with S. pneumoniae (n = 23) or saline (n = 10) and modeled the peripheral blood host response using principal components analysis and complex sparse logistic regression. Differentially expressed genes were analyzed for pathway analysis.

resultsInoculated animals developed characteristic signs and symptoms of pneumonia. A 39-gene signature was derived that classified S. pneumoniae infection with high accuracy (auROC 0.9 and 0.99 at 24 and 48 h post-inoculation, respectively). Similar performance was observed for 48-h biomarker signatures derived from peripheral blood plasma proteomic and cytokine measurements (both auROC >0.9). The gene signature retained strong diagnostic performance (auROC = 0.88) when transformed to human orthologs and applied to patients with acute respiratory illness (n = 34) or healthy controls (n = 20). Pathway analysis at 48 h identified down-regulation of mitophagy and glucocorticoid signaling in peripheral blood.

conclusionsWe report novel peripheral blood gene and protein expression signatures of S. pneumoniae pneumonia that could improve pneumonia diagnosis and found distinct pathways that may be amenable to modulation. Our findings illustrate how non-human primate models of bacterial pneumonia can successfully translate biomarker discoveries to patients.

Indexed as

PapioPneumonia, PneumococcalStreptococcus pneumoniaeAnimalsBiomarkersCytokinesDisease Models, AnimalFemaleMaleProteomicsTranscriptomeBiomarkersCytokinesanimal modelsbacterial pneumoniagene expression profilingrapid diagnostic testsStreptococcus pneumoniae

Identifiers

PMID40947770
PMCPMC12660496

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.