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The melioidosis case fatality rate is often high, and pneumonia, the most common presentation, doubles the risk of death. The alveolar macrophage is a sentinel pulmonary host defense cell, but the human alveolar macrophage in\n              <jats:italic>B. pseudomallei<\/jats:italic>\n              infection has never been studied. The objective of this study was to investigate the host-pathogen interaction of\n              <jats:italic>B. pseudomallei<\/jats:italic>\n              infection with the human alveolar macrophage and to determine the role of flagellin in modulating inflammasome-mediated pathways. We found that\n              <jats:italic>B. pseudomallei<\/jats:italic>\n              infects primary human alveolar macrophages but is gradually restricted in the setting of concurrent cell death. Electron microscopy revealed cytosolic bacteria undergoing division, indicating that\n              <jats:italic>B. pseudomallei<\/jats:italic>\n              likely escapes the alveolar macrophage phagosome and may replicate in the cytosol, where it triggers immune responses. In paired human blood monocytes, uptake and intracellular restriction of\n              <jats:italic>B. pseudomallei<\/jats:italic>\n              are similar to those observed in alveolar macrophages, but cell death is reduced. The alveolar macrophage cytokine response to\n              <jats:italic>B. pseudomallei<\/jats:italic>\n              is characterized by marked interleukin (IL)-18 secretion compared to monocytes. Both cytotoxicity and IL-18 secretion in alveolar macrophages are partially flagellin dependent. However, the proportion of IL-18 release that is driven by flagellin is greater in alveolar macrophages than in monocytes. These findings suggest differential flagellin-mediated inflammasome pathway activation in the human alveolar macrophage response to\n              <jats:italic>B. pseudomallei<\/jats:italic>\n              infection and expand our understanding of intracellular pathogen recognition by this unique innate immune lung cell.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/iai.00060-24","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T13:02:49Z","timestamp":1713186169000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Flagellin-modulated inflammasome pathways characterize the human alveolar macrophage response to\n            <i>Burkholderia pseudomallei<\/i>\n            , a lung-tropic pathogen"],"prefix":"10.1128","volume":"92","author":[{"given":"Lara","family":"Lovelace-Macon","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0177-8135","authenticated-orcid":false,"given":"Sarah M.","family":"Baker","sequence":"additional","affiliation":[{"name":"Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deirdre","family":"Ducken","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudeshna","family":"Seal","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilhem","family":"Rerolle","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Tomita","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly D.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Interfaculty Institute of Microbiology and Infection Medicine, University of Tuebingen, Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5503-7204","authenticated-orcid":false,"given":"T. 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