{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T23:23:09Z","timestamp":1769815389610,"version":"3.49.0"},"reference-count":62,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Heme oxygenases (HO) catalyze the rate-limiting step of heme degradation. The cytoprotective action of the inducible HO-1 isoform, encoded by the<jats:italic>Hmox1<\/jats:italic>gene, is required for host protection against systemic infections. Here we report that upregulation of HO-1 expression in macrophages (M\u03d5) is strictly required for protection against mycobacterial infection in mice. HO-1-deficient (<jats:italic>Hmox1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) mice are more susceptible to intravenous<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium avium<\/jats:named-content>infection, failing to mount a protective granulomatous response and developing higher pathogen loads, than infected wild-type (<jats:italic>Hmox1<\/jats:italic><jats:sup>+\/+<\/jats:sup>) controls. Furthermore,<jats:italic>Hmox1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice also develop higher pathogen loads and ultimately succumb when challenged with a low-dose aerosol infection with<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium tuberculosis<\/jats:named-content>. The protective effect of HO-1 acts independently of adaptive immunity, as revealed in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. avium<\/jats:named-content>-infected<jats:italic>Hmox1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>versus<jats:italic>Hmox1<\/jats:italic><jats:sup>+\/+<\/jats:sup>SCID mice lacking mature B and T cells. In the absence of HO-1, heme accumulation acts as a cytotoxic pro-oxidant in infected M\u03d5, an effect mimicked by exogenous heme administration to<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. avium<\/jats:named-content>-infected wild-type M\u03d5<jats:italic>in vitro<\/jats:italic>or to mice<jats:italic>in vivo<\/jats:italic>. In conclusion, HO-1 prevents the cytotoxic effect of heme in M\u03d5, contributing critically to host resistance to<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium<\/jats:named-content>infection.<\/jats:p>","DOI":"10.1128\/iai.00251-13","type":"journal-article","created":{"date-parts":[[2013,4,30]],"date-time":"2013-04-30T04:03:46Z","timestamp":1367294626000},"page":"2536-2545","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":80,"title":["Heme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium Infection"],"prefix":"10.1128","volume":"81","author":[{"given":"Sandro","family":"Silva-Gomes","sequence":"first","affiliation":[{"name":"Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Porto, Portugal"}]},{"given":"Rui","family":"Appelberg","sequence":"additional","affiliation":[{"name":"Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Porto, Portugal"}]},{"given":"Rasmus","family":"Larsen","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia, Oeiras, Portugal"}]},{"given":"Miguel Parreira","family":"Soares","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia, Oeiras, Portugal"}]},{"given":"Maria Salom\u00e9","family":"Gomes","sequence":"additional","affiliation":[{"name":"Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Porto, Portugal"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2960"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0b013e3282f9e650"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1214935"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1385\/IR:35:3:179"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00984.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2011.13"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1711.2000.00933.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1906"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1781"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2387"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2009.01424.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.7.2607"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/2063"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.61.2.748"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.010909.105600"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.03.049"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1586"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903419106"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001118"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6163"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.9.e36"},{"key":"e_1_3_3_23_2","first-page":"104","volume-title":"Methods in hematology","author":"Torrance JD","year":"1980","unstructured":"TorranceJDBothwellTH. 1980. 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