{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:09:42Z","timestamp":1790420982934,"version":"4.1.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2001,9,1]],"date-time":"2001-09-01T00:00:00Z","timestamp":999302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Advances in therapy for tuberculosis will require greater understanding of the molecular mechanisms of pathogenesis and the human immune response in this disease. Exposure of Mycobacterium tuberculosis-infected human macrophages to extracellular ATP (ATPe) results in bacterial killing, but the molecular mechanisms remain incompletely characterized. In this study, we demonstrate that ATPe-induced bactericidal activity toward virulent M. tuberculosis requires an increase in cytosolic Ca2+ in infected macrophages. Based on our previous work with primary infection of human macrophages, we hypothesized that the Ca2+ dependence of ATP-induced killing of intracellular M. tuberculosis was linked to promotion of phagosome-lysosome fusion. Using confocal laser-scanning microscopy, we demonstrate that ATPe induces fusion of the M. tuberculosis-containing phagosome with lysosomes, defined by accumulation of three lysosomal proteins and an acidophilic dye. Stimulation of phagosome-lysosome fusion by ATPe exhibited distinct requirements for both Ca2+ and phospholipase D and was highly correlated with killing of intracellular bacilli. Thus, key signal transduction pathways are conserved between two distinct models of human macrophage antituberculous activity: primary infection of naive macrophages and physiologic stimulation of macrophages stably infected with M. tuberculosis.<\/jats:p>","DOI":"10.4049\/jimmunol.167.6.3308","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T19:30:26Z","timestamp":1398022226000},"page":"3308-3315","source":"Crossref","is-referenced-by-count":116,"title":["ATP Stimulates Human Macrophages to Kill Intracellular Virulent\n                    <i>Mycobacterium tuberculosis<\/i>\n                    Via Calcium-Dependent Phagosome-Lysosome Fusion"],"prefix":"10.1093","volume":"167","author":[{"given":"David J","family":"Kusner","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Iowa and Veterans Affairs Medical Center , Iowa City, IA 52242"},{"name":"Inflammation Program, University of Iowa and Veterans Affairs Medical Center , Iowa City, IA 52242"},{"name":"Graduate Program in Immunology, University of Iowa and Veterans Affairs Medical Center , Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A","family":"Barton","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Iowa and Veterans Affairs Medical Center , Iowa City, IA 52242"},{"name":"Inflammation Program, University of Iowa and Veterans Affairs Medical Center , Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2001,9,15]]},"reference":[{"key":"2026020208064051400_R1","first-page":"905","volume-title":"Infect. 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