Age-related dysregulation of CXCL9/10 in monocytes is linked to impaired innate immune responses in a mouse model of Staphylococcus aureus osteomyelitis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39001897", "kind": "science-record", "revision": 4, "content_hash": "sha256:0665a339afd0b6155bb1435da61d508762fc8b5cd1a5933e02ee94b312db604f", "created_at": "2026-11-01T20:29:04Z", "updated_at": "2026-11-01T22:54:41Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Age-related dysregulation of CXCL9/10 in monocytes is linked to impaired innate immune responses in a mouse model of Staphylococcus aureus osteomyelitis.", "doi": "10.1007/s00018-024-05311-2", "pmid": "39001897", "authors": ["Yihuang Lin", "Mankai Yang", "Chubin Cheng", "Jichang Wu", "Bin Yu", "Xianrong Zhang"], "journal": "Cellular and molecular life sciences : CMLS", "year": 2024, "abstract": "BACKGROUND: Age-associated impairments in innate immunity are believed to be a causative factor responsible for severe pathogenesis of Staphylococcus aureus (S. aureus) infection in the bone tissue. However, the basis for age-associated decline in innate immune response upon S. aureus infection remains poorly understood.\nRESULTS: Our transcriptional data (GEO: GSE166522) from a mouse model of S. aureus osteomyelitis show up-regulated CXCL9 and CXCL10 (CXCL9/10), which is further confirmed in vitro and in vivo by the present study. Notably, monocytes are a main source for CXCL9/10 production in bone marrow upon S. aureus challenge, but this response declines in middle-aged mice. Interestingly, conditional medium of bone marrow monocytes from middle-aged mice has a strikingly decreased effect on bactericidal functions of neutrophils and macrophages compares with that from young mice. We further show that activation of CXCL9/10-CXCR3 axis between monocytes and macrophages/neutrophils promotes the bactericidal function of the cells, whereas blocking the axis impairs such function. Importantly, treatment with either exogenous CXCL9 or CXCL10 in a middle-aged mice model enhances, while pharmacological inhibition of CXCR3 in young mice model impairs, bacterial clearance and bone marrow structure.\nCONCLUSIONS: These findings demonstrate that bone marrow monocytes act as a critical promotor of innate immune response via the CXLCL9/10-CXCR3 axis upon S. aureus infection, and that the increased susceptibility to S. aureus infection in skeleton in an aged host may be largely attributable to the declined induction of CXCR9/10 in monocytes.", "claims": [{"id": "claim-method", "statement": "If the data were in accordance with normal distribution and homogeneity of variance, the Student’s t test was used to compare the statistical differences between the two groups. One-way analysis of variance (One-way ANVOA) with Bonferroni or Dunnett’s T3 post hoc test was used for statistical comparison of more than two groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39001897", "locator": "sections[14] \"Statistical analysis\" paragraph 2", "quote": "If the data were in accordance with normal distribution and homogeneity of variance, the Student’s t test was used to compare the statistical differences between the two groups. One-way analysis of variance (One-way ANVOA) with Bonferroni or Dunnett’s T3 post hoc test was used for statistical comparison of more than two groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analyzed during this study are included in this published article and its supplementary information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39001897", "locator": "sections[29] \"notes\" paragraph 1", "quote": "All data generated or analyzed during this study are included in this published article and its supplementary information files."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Monocyte-derived CXCL9/10 enhances the bactericidal function of neutrophils and macrophages through the CXCL9/10-CXCR3 axis, and reduced CXCL9/10 production in middle-aged monocytes contributes to impaired bacterial clearance.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39001897", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "These findings demonstrate that bone marrow monocytes act as a critical promotor of innate immune response via the CXLCL9/10-CXCR3 axis upon S. aureus infection, and that the increased susceptibility to S. aureus infection in skeleton in an aged host may be largely attributable to the declined induction of CXCR9/10 in monocytes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Monocyte-derived CXCL9/10 enhances the bactericidal function of neutrophils and macrophages through the CXCL9/10-CXCR3 axis, and reduced CXCL9/10 production in middle-aged monocytes contributes to impaired bacterial clearance.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:39001897"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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