{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T03:39:12Z","timestamp":1783654752925,"version":"3.55.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"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":"<jats:p>\n                    Immune checkpoint blockade (ICB) has revolutionized cancer therapy, yet its unintended impact on chronic infections remains poorly understood. Here, we identify PD-L1 expression on CD14\n                    <jats:sup>-<\/jats:sup>\n                    CD16\n                    <jats:sup>+<\/jats:sup>\n                    monocytes as a critical determinant for preventing early tuberculosis (TB) progression. By integrating real-world adverse event data, Mendelian randomization (MR), and transcriptomic analysis, we establish a causal and cell-specific link between PD-L1 downregulation and early TB progression. Analysis of the FAERS database revealed that the PD-L1 inhibitor durvalumab is significantly associated with TB-related adverse events (reporting odds ratio = 7.81; 95% CI: 4.43-13.78;\n                    <jats:italic>P<\/jats:italic>\n                    = 1.10\u00d710\n                    <jats:sup>-18<\/jats:sup>\n                    ). MR analysis confirmed that genetically elevated PD-L1 expression in CD14\n                    <jats:sup>-<\/jats:sup>\n                    CD16\n                    <jats:sup>+<\/jats:sup>\n                    monocytes confers protection against early TB progression (OR = 0.918,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.042), independent of confounding or reverse causality. Transcriptomic profiling revealed that PD-L1\n                    <jats:sup>high<\/jats:sup>\n                    CD14\n                    <jats:sup>-<\/jats:sup>\n                    CD16\n                    <jats:sup>+<\/jats:sup>\n                    monocytes exhibit enhanced antigen surveillance, whereas PD-L1\n                    <jats:sup>low<\/jats:sup>\n                    cells display metabolic reprogramming associated with immune escape. Upstream regulatory analysis identified CDAN1, TCOF1, and LMO2 as transcriptional drivers of PD-L1, enriched in high-risk individuals. In\n                    <jats:italic>silico<\/jats:italic>\n                    drug prediction and molecular docking suggested several PD-L1-modulating compounds, including ruthenium, pomalidomide, zidovudine, and lycorine. Notably, several of these compounds (e.g., ruthenium complexes, pomalidomide, aziridine) have reported anti-mycobacterial effects, which supports the reliability of our screening results and their potential relevance to TB regulation.\n                    <jats:italic>In vitro<\/jats:italic>\n                    validation demonstrated that lycorine dose-dependently upregulates PD-L1 and inhibits\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    reactivation. Together, our findings define a mechanistic axis in CD14\n                    <jats:sup>-<\/jats:sup>\n                    CD16\n                    <jats:sup>+<\/jats:sup>\n                    monocytes that underpins early TB control and is vulnerable to PD-L1 blockade. Collectively, these findings align with the established notion that assessing latent tuberculosis infection before initiating immune-modulating therapies is essential for minimizing reactivation risk, and propose tractable molecular targets for preventing TB reactivation in immunocompromised hosts.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2025.1684030","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T06:30:16Z","timestamp":1765261816000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["CD14- CD16+ monocyte PD-L1 prevents early tuberculosis progression and constrains reactivation under immune checkpoint therapy"],"prefix":"10.3389","volume":"15","author":[{"given":"Wentao","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxaio","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengjun","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.875910","article-title":"Multidisciplinary approach to treatment with immune checkpoint inhibitors in patients with HIV, tuberculosis, or underlying autoimmune diseases","volume":"9","author":"Aguilar-Company","year":"2022","journal-title":"Front. 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