{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:04:03Z","timestamp":1791223443816,"version":"4.1.0"},"reference-count":64,"publisher":"National Academy of Sciences","issue":"38","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2014,9,23]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Tuberculosis (TB) granulomas represent sites of both bacterial containment and tissue pathology. Macrophage killing of\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (\n                    <jats:italic>Mtb<\/jats:italic>\n                    ) in granulomas to contain infection must be regulated to prevent collateral tissue damage. Nitric oxide synthase-2 (NOS2) and arginase-1 (Arg1), macrophage enzymes metabolizing\n                    <jats:sc>l<\/jats:sc>\n                    -arginine, play key roles in this process. NOS2 produces reactive nitrogen intermediates to kill\n                    <jats:italic>Mtb<\/jats:italic>\n                    , whereas Arg1 regulates NOS2 activity via substrate competition. Arg1 activity could predominate in hypoxic regions of granulomas where NOS2 activity likely is suboptimal. Here we show that Arg1 plays a central role in restricting bacterial growth and restraining tissue damage within granulomas in TB and other chronic inflammatory diseases. These findings point to the modulation of Arg1 activity as a potential host-directed therapy for TB.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1408839111","type":"journal-article","created":{"date-parts":[[2014,9,9]],"date-time":"2014-09-09T00:38:33Z","timestamp":1410223113000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":115,"title":["Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas"],"prefix":"10.1073","volume":"111","author":[{"given":"Mar\u00eda A.","family":"Duque-Correa","sequence":"first","affiliation":[{"name":"Department of Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja A.","family":"K\u00fchl","sequence":"additional","affiliation":[{"name":"Department of Immunopathology, Charit\u00e9 - University Medicine Berlin, 12200 Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo C.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Zedler","sequence":"additional","affiliation":[{"name":"Department of Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Schommer-Leitner","sequence":"additional","affiliation":[{"name":"Department of Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"January","family":"Weiner","sequence":"additional","affiliation":[{"name":"Department of Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Hurwitz","sequence":"additional","affiliation":[{"name":"Central Support Unit Biochemistry, Max Planck Institute for Infection Biology, 10117 Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph E.","family":"Qualls","sequence":"additional","affiliation":[{"name":"Departments of eInfectious Diseases and"},{"name":"Immunology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A.","family":"Kosmiadi","sequence":"additional","affiliation":[{"name":"Immunology and Thoracic Surgery, Central Tuberculosis Research Institute, Moscow 107564, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Murray","sequence":"additional","affiliation":[{"name":"Departments of eInfectious Diseases and"},{"name":"Immunology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan H. E.","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Department of Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen T.","family":"Reece","sequence":"additional","affiliation":[{"name":"Department of Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2014,9,8]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3211"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2011.10.006"},{"key":"e_1_3_3_3_2","first-page":"1","article-title":"The granulomatous inflammatory exudate","volume":"8","author":"Spector WG","year":"1969","unstructured":"WG Spector, The granulomatous inflammatory exudate. Int Rev Exp Pathol 8, 1\u201355 (1969).","journal-title":"Int Rev Exp Pathol"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.12.032"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2009.01424.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1538"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00994.x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2011.14"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1781"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00915.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300113"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3073"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2007.09.008"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1004"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1001-907"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132532"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021186"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.10.5243"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1167452"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.4110\/in.2009.9.2.46"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2008.04.003"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1671"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201545"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2000955"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803567"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.4399"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1668"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00608.x"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/683485"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000371"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-3416fje"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000480"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-010-0630-3"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2012.07.005"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2005.01.008"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003771"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42796"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2012.01012.x"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.66.6.889"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1998.274.3.R775"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200309-1304OC"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-9966-30-95"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1628"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1906"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.12.7099-7108.2003"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001847"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0710409"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1303048"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13490"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080669"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3412"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(08)70184-1"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.10.6298"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.8.4653-4657.2000"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.11.6533"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061961"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001684"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2010.09.003"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2004.09.002"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902009"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1086\/430621"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-4505"},{"key":"e_1_3_3_63_2","unstructured":"Pinheiro J Bates D DebRoy S Sarkar D and R Development Core Team (2013) nlme: Linear and nonlinear mixed effects models. R package. Version 3.1-109. (R Development Core Team Vienna)."},{"key":"e_1_3_3_64_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4419-0318-1","volume-title":"Mixed Effects Models in S and S-plus","author":"Pinheiro J","year":"2000","unstructured":"J Pinheiro, D Bates Mixed Effects Models in S and S-plus (Springer, 1st Ed, New York), pp. 1\u2013528 (2000).","edition":"1"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1408839111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T23:17:37Z","timestamp":1649805457000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1408839111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,8]]},"references-count":64,"journal-issue":{"issue":"38","published-print":{"date-parts":[[2014,9,23]]}},"alternative-id":["10.1073\/pnas.1408839111"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1408839111","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,8]]},"assertion":[{"value":"2014-09-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}