{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T23:17:30Z","timestamp":1789082250549,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012979","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000}}],"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Theme-Based Research Scheme","award":["T11-104\/22-R"],"award-info":[{"award-number":["T11-104\/22-R"]}]},{"name":"the Research Impact Fund","award":["R1011-23"],"award-info":[{"award-number":["R1011-23"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Klebsiella pneumoniae<\/jats:italic> (<jats:italic>Kp<\/jats:italic>) is responsible for a wide range of infections, including pneumonia, sepsis, and urinary tract infections. However, the treatment options are limited due to the continuous evolution of drug-resistant and hypervirulent variants. It is crucial to investigate the mechanisms behind the high mortality rate of hypervirulent <jats:italic>Kp<\/jats:italic> (hv<jats:italic>Kp<\/jats:italic>) strains to develop new strategies for preventing hv<jats:italic>Kp<\/jats:italic> from evading the host\u2019s defenses and improving treatment effectiveness for these fatal infections. In this study, we used a hv<jats:italic>Kp<\/jats:italic>-induced mouse bacteremia model and performed single-cell RNA sequencing to investigate the effects of hv<jats:italic>Kp<\/jats:italic> infection. Our findings demonstrated that hv<jats:italic>Kp<\/jats:italic> infection led to a decrease in lymphocytes (lymphopenia), attributed to impaired proliferation and apoptosis. The infiltration of myeloid-derived suppressor cells (MDSCs) in the infected lungs was confirmed to suppress T cell proliferation, leading to lymphopenia. We further identified that hv<jats:italic>Kp<\/jats:italic> promotes tryptophan metabolism in infected lungs, enhancing the immunosuppressive activity of MDSCs by inducing the production of the enzyme IDO1. Our <jats:italic>ex vivo<\/jats:italic> inhibition experiment revealed that L-kynurenine, a product of tryptophan metabolism, inhibits T-cell proliferation and induces T-cell apoptosis, further suppressing T-cell mediated responses against bacteria. Importantly, when we knocked out the <jats:italic>Ido1<\/jats:italic> gene or inhibited IDO1 expression using a specific inhibitor 1-MT in mice, we observed a significant enhancement in T-cell mediated responses against hv<jats:italic>Kp<\/jats:italic>. These findings highlight the crucial role of MDSCs in hv<jats:italic>Kp<\/jats:italic>-induced bacteremia and suggest a promising immunotherapeutic approach by inhibiting IDO1 production to combat infectious diseases.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012979","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T17:22:40Z","timestamp":1742232160000},"page":"e1012979","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Myeloid-derived suppressor cell inhibits T-cell-based defense against Klebsiella pneumoniae infection via IDO1 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