{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:16:44Z","timestamp":1791667004549,"version":"4.3.4"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"\n Background<\/jats:title>\n \n The host\u2019s immune status is a critical determinant of the pathogen profile in pulmonary infections, but quantitative indicators to delineate this dynamic association are lacking. This study aimed to use CD4\n +<\/jats:sup>\n T cells count as an objective parameter to systematically characterize the evolution of the pathogen profile in bronchoalveolar lavage fluid-targeted next-generation sequencing (BALF-tNGS) from patients with severe pneumonia.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We retrospectively analyzed 286 adult patients who underwent BALF-tNGS for severe pneumonia. Patients were stratified into four strata based on CD4\n +<\/jats:sup>\n T cells count: severe immunosuppression, moderate immunosuppression, low-normal immunity, and immunocompetent. Cochran-Armitage trend test, cluster analysis, and Kruskal-Wallis test were used to analyze the associations between CD4\n +<\/jats:sup>\n T cells strata and pathogen detection rates\/co-infection complexity.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The detection rates of\n Pneumocystis jirovecii<\/jats:italic>\n (\n PJP<\/jats:italic>\n ) and Cytomegalovirus (CMV) showed a highly significant increasing trend with decreasing CD4\n +<\/jats:sup>\n T cells strata (\n p<\/jats:italic>\n &lt; 0.05). CD4\n +<\/jats:sup>\n T cells count &lt; 100 cells\/\u03bcL was the most significant risk factor for PJP infection (detection rate 39.6%). Meanwhile, as the CD4\n +<\/jats:sup>\n T cells count decreased, the number of pathogen species detected in the patient\u2019s BALF significantly increased, with a statistically significant difference between groups (\n p<\/jats:italic>\n &lt; 0.05). The median number in the severe immunosuppression stratum was significantly higher than that in the immunocompetent stratum.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The CD4\n +<\/jats:sup>\n T cells count quantitatively defines the pathogen ecology in pulmonary infections. A CD4\n +<\/jats:sup>\n T cells count &lt; 100 cells\/\u03bcL represents a critical threshold for opportunistic infections and complex co-infections. These findings support the integration of CD4\n +<\/jats:sup>\n T cells counting into the initial assessment framework for severe pneumonia to guide precise empirical therapy and diagnostic strategies.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1742311","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T06:43:16Z","timestamp":1766040196000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["CD4+ T cells stratification unveils a dynamic pathogen landscape in severe pneumonia: a targeted next-generation sequencing-based cohort study"],"prefix":"10.3389","volume":"15","author":[{"given":"Shuaishuai","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Che","family":"Lihe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhang","family":"Minglei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2024.13277","article-title":"Clinical diagnostic value of targeted next-generation sequencing for infectious diseases (Review)","volume":"30","author":"Chen","year":"2024","journal-title":"Mol. 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