ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Clinical Infectious Diseases
CD4+ T cells Stratification Unveils a Dynamic Pathogen Landscape in Severe Pneumonia: A Targeted Next-generation Sequencing-Based Cohort Study
Provisionally accepted
- 1China-Japan Union Hospital, Jilin University, Changchun, China
- 2Jilin University First Hospital, changchun, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background The host's 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+ 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. Methods We retrospectively analyzed 286 adult patients who underwent BALF-tNGS for severe pneumonia. Patients were stratified into four strata based on CD4+ 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+ T cells strata and pathogen detection rates/co-infection complexity. Results The detection rates of Pneumocystis jirovecii (PJP) and Cytomegalovirus (CMV) showed a highly significant increasing trend with decreasing CD4+ T cells strata (p<0.05). CD4+ T cells count < 100 cells/μL was the most significant risk factor for PJP infection (detection rate 39.6%). Meanwhile, as the CD4+ T cells count decreased, the number of pathogen species detected in the patient's BALF significantly increased, with a statistically significant difference between groups (p < 0.05). The median number in the severe immunosuppression stratum was significantly higher than that in the immunocompetent stratum. Conclusion The CD4+ T cells count quantitatively defines the pathogen ecology in pulmonary infections. A CD4+ T cells count < 100 cells/μL represents a critical threshold for opportunistic infections and complex co-infections. These findings support the integration of CD4+ T cells counting into the initial assessment framework for severe pneumonia to guide precise empirical therapy and diagnostic strategies.
Keywords: BALF, CD4, Infection, Severe pneumonia, TNGS
Received: 08 Nov 2025; Accepted: 01 Dec 2025.
Copyright: © 2025 Wang, Yu, Lihe, Sun, DU and Minglei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
NA DU
Zhang Minglei
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.