{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T18:03:54Z","timestamp":1780682634142,"version":"3.54.1"},"reference-count":26,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100008809","name":"University of Hail","doi-asserted-by":"publisher","award":["BA-24 029"],"award-info":[{"award-number":["BA-24 029"]}],"id":[{"id":"10.13039\/501100008809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the association between ICU-acquired infections and 28-day mortality in pneumonia-induced sepsis and to explore associated immune-related gene expression patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A secondary analysis was performed using the publicly available GSE65682 dataset, including adult ICU patients with sepsis secondary to community-acquired pneumonia (CAP) or hospital-acquired pneumonia (HAP). Patients were stratified based on the development of ICU-acquired infections. 28-day mortality and whole-blood leukocyte gene expression at ICU admission were compared between groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 144 patients, 20 developed ICU-acquired infections. In the CAP subgroup, ICU-acquired infections were associated with numerically higher 28-day mortality compared to those without infection (45.5% vs. 18.2%, p\u2009=\u20090.05), although this finding should be interpreted with caution given the retrospective study design and limited sample size. In HAP patients, a similar pattern was not observed (22.2% vs. 19.6%). Transcriptomic analysis showed significant downregulation of the interleukin-7 receptor (IL7R) in CAP patients who developed ICU-acquired infections, with PRKACB and CD3D also demonstrating a downward trend.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that early immune dysregulation may be associated with an increased susceptibility to secondary infections and potentially worse outcomes among CAP patients. IL7R may represent a candidate signal of immune dysregulation and warrants further investigation and validation in future studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0349871","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:31:11Z","timestamp":1780680671000},"page":"e0349871","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["ICU-acquired infections and mortality in community-acquired pneumonia\u2013induced sepsis: Insights from a transcriptomic analysis"],"prefix":"10.1371","volume":"21","author":[{"given":"Sultan","family":"Almuntashiri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazed S.","family":"Alsowaida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Alghubayshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muteb","family":"Alanazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4245-0482","authenticated-orcid":true,"given":"Tareq Nafea","family":"Alharby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5247-6356","authenticated-orcid":true,"given":"Mukhtar","family":"Ansari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"issue":"9","key":"pone.0349871.ref001","doi-asserted-by":"crossref","first-page":"3188","DOI":"10.3390\/jcm12093188","article-title":"2023 update on sepsis and septic shock in adult patients: Management in the emergency department","volume":"12","author":"M Guarino","year":"2023","journal-title":"J Clin Med"},{"issue":"6","key":"pone.0349871.ref002","doi-asserted-by":"crossref","DOI":"10.3390\/pathogens13060461","article-title":"Hospital acquired sepsis, disease prevalence, and recent advances in sepsis mitigation","volume":"13","author":"M Garvey","year":"2024","journal-title":"Pathogens"},{"key":"pone.0349871.ref003","doi-asserted-by":"crossref","first-page":"628302","DOI":"10.3389\/fmed.2021.628302","article-title":"Sepsis-pathophysiology and therapeutic concepts","volume":"8","author":"D Jarczak","year":"2021","journal-title":"Front Med (Lausanne)"},{"issue":"1","key":"pone.0349871.ref004","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1111\/imr.12499","article-title":"The immune system\u2019s role in sepsis progression, resolution, and long-term outcome","volume":"274","author":"MJ Delano","year":"2016","journal-title":"Immunol Rev"},{"key":"pone.0349871.ref005","doi-asserted-by":"crossref","first-page":"104335","DOI":"10.1016\/j.ebiom.2022.104335","article-title":"Host-targeted approaches to sepsis due to community-acquired pneumonia","volume":"86","author":"C Cilloniz","year":"2022","journal-title":"EBioMedicine"},{"issue":"5","key":"pone.0349871.ref006","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1093\/bjaed\/mkv052","article-title":"Severe community-acquired pneumonia","volume":"16","author":"AJ Morgan","year":"2016","journal-title":"BJA Educ"},{"issue":"1","key":"pone.0349871.ref007","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1186\/s12879-025-11027-w","article-title":"Incidence and risk factor of sepsis in patients with severe community-acquired pneumonia: A Chinese, single-center, retrospective study","volume":"25","author":"X Wang","year":"2025","journal-title":"BMC Infect Dis"},{"key":"pone.0349871.ref008","doi-asserted-by":"crossref","first-page":"962470","DOI":"10.3389\/fcimb.2022.962470","article-title":"Clinical characteristics and risk factors associated with ICU-acquired infections in sepsis: A retrospective cohort study","volume":"12","author":"Y He","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"issue":"3","key":"pone.0349871.ref009","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1007\/s00134-023-07295-2","article-title":"ICU-acquired infections in immunocompromised patients","volume":"50","author":"L Kreitmann","year":"2024","journal-title":"Intensive Care Med"},{"issue":"1","key":"pone.0349871.ref010","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1186\/s12889-021-10857-y","article-title":"Survival rate in patients with ICU-acquired infections and its related factors in Iran\u2019s hospitals","volume":"21","author":"Medsk Etemad","year":"2021","journal-title":"BMC Public Health"},{"issue":"10","key":"pone.0349871.ref011","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.3390\/biomedicines11102755","article-title":"A systematic review of gene expression studies in critically ill patients with sepsis and community-acquired pneumonia","volume":"11","author":"D Viasus","year":"2023","journal-title":"Biomedicines"},{"issue":"7","key":"pone.0349871.ref012","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1164\/rccm.201502-0355OC","article-title":"A molecular biomarker to diagnose community-acquired pneumonia on intensive care unit admission","volume":"192","author":"BP Scicluna","year":"2015","journal-title":"Am J Respir Crit Care Med"},{"issue":"11","key":"pone.0349871.ref013","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1002\/eji.201646809","article-title":"Ablation of the C\u03b22 subunit of PKA in immune cells leads to increased susceptibility to systemic inflammation in mice","volume":"47","author":"LV Moen","year":"2017","journal-title":"Eur J Immunol"},{"key":"pone.0349871.ref014","doi-asserted-by":"crossref","first-page":"4911","DOI":"10.2147\/JIR.S519885","article-title":"Biological functions and clinical implications of CFLAR: From Cell death mechanisms to therapeutic targeting in immune regulation","volume":"18","author":"H Zhang","year":"2025","journal-title":"J Inflamm Res"},{"key":"pone.0349871.ref015","doi-asserted-by":"crossref","first-page":"116441","DOI":"10.1016\/j.bcp.2024.116441","article-title":"Key links in the physiological regulation of the immune system and disease induction: T cell receptor -CD3 complex","volume":"227","author":"D Liu","year":"2024","journal-title":"Biochem Pharmacol"},{"issue":"1","key":"pone.0349871.ref016","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1161\/HYPERTENSIONAHA.122.19431","article-title":"TSG-6 (Tumor Necrosis Factor-\u03b1-Stimulated Gene\/Protein-6): An emerging remedy for renal inflammation","volume":"80","author":"Y Jiang","year":"2023","journal-title":"Hypertension"},{"issue":"1","key":"pone.0349871.ref017","doi-asserted-by":"crossref","first-page":"7268","DOI":"10.1038\/s41467-021-27197-5","article-title":"Interleukin-7 receptor \u03b1 mutational activation can initiate precursor B-cell acute lymphoblastic leukemia","volume":"12","author":"ARM Almeida","year":"2021","journal-title":"Nat Commun"},{"key":"pone.0349871.ref018","doi-asserted-by":"crossref","first-page":"1545760","DOI":"10.3389\/fimmu.2025.1545760","article-title":"IL-7 in autoimmune diseases: Mechanisms and therapeutic potential","volume":"16","author":"Z Zeng","year":"2025","journal-title":"Front Immunol"},{"issue":"11","key":"pone.0349871.ref019","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1097\/CCM.0000000000003281","article-title":"Low interleukin-7 receptor messenger RNA expression is independently associated with day 28 mortality in septic shock patients","volume":"46","author":"B Delwarde","year":"2018","journal-title":"Crit Care Med"},{"issue":"5","key":"pone.0349871.ref020","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.98960","article-title":"Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial","volume":"3","author":"B Francois","year":"2018","journal-title":"JCI Insight"},{"issue":"1","key":"pone.0349871.ref021","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s13613-023-01109-w","article-title":"Intravenously administered interleukin-7 to reverse lymphopenia in patients with septic shock: A double-blind, randomized, placebo-controlled trial","volume":"13","author":"T Daix","year":"2023","journal-title":"Ann Intensive Care"},{"issue":"1","key":"pone.0349871.ref022","doi-asserted-by":"crossref","first-page":"13145","DOI":"10.1038\/s41598-022-13063-x","article-title":"IL-7\/IL7R axis dysfunction in adults with severe community-acquired pneumonia (CAP): A cross-sectional study","volume":"12","author":"S Ampuero","year":"2022","journal-title":"Sci Rep"},{"key":"pone.0349871.ref023","doi-asserted-by":"crossref","first-page":"829","DOI":"10.2147\/JIR.S301663","article-title":"Screening of key genes of sepsis and septic shock using bioinformatics analysis","volume":"14","author":"X Zeng","year":"2021","journal-title":"J Inflamm Res"},{"key":"pone.0349871.ref024","doi-asserted-by":"crossref","first-page":"814240","DOI":"10.3389\/fmolb.2022.814240","article-title":"Diagnostic Potential of Plasma Extracellular Vesicle miR-483-3p and Let-7d-3p for Sepsis","volume":"9","author":"G Qiu","year":"2022","journal-title":"Front Mol Biosci"},{"issue":"29","key":"pone.0349871.ref025","doi-asserted-by":"crossref","DOI":"10.1097\/MD.0000000000034295","article-title":"CD3D and CD247 are the molecular targets of septic shock","volume":"102","author":"Q Yang","year":"2023","journal-title":"Medicine (Baltimore)"},{"issue":"10","key":"pone.0349871.ref026","article-title":"Identification of diagnostic candidate genes in COVID-19 patients with sepsis","volume":"12","author":"J Li","year":"2024","journal-title":"Immun Inflamm Dis"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0349871","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:31:16Z","timestamp":1780680676000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0349871"}},"subtitle":[],"editor":[{"given":"Gurmeet","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,5]]},"references-count":26,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0349871","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,5]]}}}