{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T16:39:08Z","timestamp":1777048748622,"version":"3.51.4"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Pulmonary\n                      <jats:italic>Mycobacteroides abscessus<\/jats:italic>\n                      (MAB) infection presents a therapeutic challenge, and while anti-programmed cell death protein 1(PD-1) therapy is clinically associated with increased MAB risk, yet the underlying immunomodulatory mechanisms remain elusive.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We established a PD-1-deficient mouse model of MAB infection and assessed bacterial clearance, immune responses, and metabolic alterations using colony counting, histopathology, flow cytometry, multiplex immunofluorescence, transcriptomics, and metabolic assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PD-1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice showed increased susceptibility to MAB. Early infection was marked by elevated lung CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells (Th17\/Treg), diminished Th1 cells and neutrophils, and increased blood cytokines (IFN-\u03b3, IL-21, IL-6, IL-27). Late infection featured further Th1 reduction, neutrophil accumulation, and NETs activation (H3cit, NE-DNA, MPO), along with reduced CXCL9 but elevated IL-6, IL-21, IL-27, CXCL10, and S100A8 in blood. Metabolic changes included decreased blood glucose, elevated lung ATP, and upregulation of HIF-1 pathway proteins (e.g., HK2, iNOS).\n                      <jats:italic>In vitro<\/jats:italic>\n                      , PD-1 deficiency suppressed glycolysis in T cells yet augmented it in neutrophils upon MAB infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PD-1 deficiency disrupts T cell\u2013neutrophil crosstalk via metabolic reprogramming, resulting in immune dysregulation and exacerbated infection. These findings underscore infection risks linked to PD-1\/PD-L1 blockade, informing clinical safety and therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1803806","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T15:50:30Z","timestamp":1777045830000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["PD-1 deficiency exacerbates Mycobacteroides abscessus lung infection via metabolic rewiring and dysregulated neutrophil\/T cell responses"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaowen","family":"Yu","sequence":"first","affiliation":[{"name":"Institute of Modern Biopharmaceuticals, School of Life Sciences, Southwest University","place":["Chongqing, China"]},{"name":"Basic Research Laboratory of Traditional Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing University of Chinese 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