{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:33:03Z","timestamp":1790163183119,"version":"4.1.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["P01 HL114453, R01 HL136143, R01 HL142084, K24 HL14285"],"award-info":[{"award-number":["P01 HL114453, R01 HL136143, R01 HL142084, K24 HL14285"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI129976"],"award-info":[{"award-number":["R01 AI129976"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["IK2 BX004886, I01 CX001562"],"award-info":[{"award-number":["IK2 BX004886, I01 CX001562"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p><jats:italic>Klebsiella pneumoniae<\/jats:italic> (<jats:italic>Kp<\/jats:italic>) is a common cause of hospital-acquired pneumonia. Although previous studies have suggested that evasion of phagocytic uptake is a virulence determinant of <jats:italic>Kp<\/jats:italic>, few studies have examined phagocytosis sensitivity in clinical <jats:italic>Kp<\/jats:italic> isolates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We screened 19 clinical respiratory <jats:italic>Kp<\/jats:italic> isolates that were previously assessed for mucoviscosity for their sensitivity to macrophage phagocytic uptake, and evaluated phagocytosis as a functional correlate of <jats:italic>in vivo Kp<\/jats:italic> pathogenicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The respiratory <jats:italic>Kp<\/jats:italic> isolates displayed heterogeneity in the susceptibility to macrophage phagocytic uptake, with 14 out of 19 <jats:italic>Kp<\/jats:italic> isolates displaying relative phagocytosis-sensitivity compared to the reference <jats:italic>Kp<\/jats:italic> strain ATCC 43816, and 5 out of 19 <jats:italic>Kp<\/jats:italic> isolates displaying relative phagocytosis-resistance. Intratracheal infection with the non-mucoviscous phagocytosis-sensitive isolate S17 resulted in a significantly lower bacterial burden compared to infection with the mucoviscous phagocytosis-resistant isolate W42. In addition, infection with S17 was associated with a reduced inflammatory response, including reduced bronchoalveolar lavage fluid (BAL) polymorphonuclear (PMN) cell count, and reduced BAL TNF, IL-1\u03b2, and IL-12p40 levels. Importantly, host control of infection with the phagocytosis-sensitive S17 isolate was impaired in alveolar macrophage (AM)-depleted mice, whereas AM-depletion had no significant impact on host defense against infection with the phagocytosis-resistant W42 isolate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Altogether, these findings show that phagocytosis is a primary determinant of pulmonary clearance of clinical <jats:italic>Kp<\/jats:italic> isolates.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2023.1150658","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T04:47:11Z","timestamp":1679978831000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Phagocytosis is a primary determinant of pulmonary clearance of clinical Klebsiella pneumoniae isolates"],"prefix":"10.3389","volume":"13","author":[{"given":"Rick","family":"van der Geest","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongye","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hern\u00e1n F.","family":"Pe\u00f1aloza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G.","family":"Bain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naina","family":"Kohli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Larson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara L. 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