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The granuloma's main function is to constrain and prevent dissemination of the mycobacteria while focusing the immune response to a limited area. In some cases these lesions can grow progressively into large granulomas which can undergo central necrosis, thereby leading to their caseation. Macrophages are the most abundant cells present in the granuloma and are known to adapt under hypoxic conditions in order to avoid cell death. Our laboratory has developed a granuloma necrosis model that mimics the human pathology of\n            <jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>\n            , using C57BL\/6 mice infected intravenously with a low dose of a highly virulent strain of\n            <jats:named-content content-type=\"genus-species\">Mycobacterium avium<\/jats:named-content>\n            . In this work, a mouse strain deleted of the hypoxia inducible factor 1\u03b1 (HIF-1\u03b1) under the Cre-lox system regulated by the lysozyme M gene promoter was used to determine the relevance of HIF-1\u03b1 in the caseation of granulomas. The genetic ablation of HIF-1\u03b1 in the myeloid lineage causes the earlier emergence of granuloma necrosis and clearly induces an impairment of the resistance against\n            <jats:named-content content-type=\"genus-species\">M. avium<\/jats:named-content>\n            infection coincident with the emergence of necrosis. The data provide evidence that granulomas become hypoxic before undergoing necrosis through the analysis of vascularization and quantification of HIF-1\u03b1 in a necrotizing mouse model. Our results show that interfering with macrophage adaptation to hypoxia, such as through HIF-1\u03b1 inactivation, accelerates granuloma necrosis.\n          <\/jats:p>","DOI":"10.1128\/iai.00144-15","type":"journal-article","created":{"date-parts":[[2015,6,23]],"date-time":"2015-06-23T01:31:23Z","timestamp":1435023083000},"page":"3534-3544","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":39,"title":["Lack of the Transcription Factor Hypoxia-Inducible Factor 1\u03b1 (HIF-1\u03b1) in Macrophages Accelerates the Necrosis of Mycobacterium avium-Induced Granulomas"],"prefix":"10.1128","volume":"83","author":[{"given":"Marcos S.","family":"Cardoso","sequence":"first","affiliation":[{"name":"Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal"}]},{"given":"T\u00e2nia M.","family":"Silva","sequence":"additional","affiliation":[{"name":"Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"}]},{"given":"Mariana","family":"Resende","sequence":"additional","affiliation":[{"name":"Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal"},{"name":"ICVS\/3B's\u2013PT Government Associate Laboratory, Braga, Portugal"}]},{"given":"Rui","family":"Appelberg","sequence":"additional","affiliation":[{"name":"Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6035-4095","authenticated-orcid":false,"given":"Margarida","family":"Borges","sequence":"additional","affiliation":[{"name":"Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal"},{"name":"UCIBIO\/REQUIMTE, Departamento de Ci\u00eancias Biol\u00f3gicas, Laborat\u00f3rio de Bioqu\u00edmica, Faculdade de Farm\u00e1cia da Universidade do Porto, Porto, Portugal"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2014.09.009"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(98)01209-8"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010515"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir786"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.4399"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.6.2243"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90001-2"},{"key":"e_1_3_3_9_2","first-page":"250","article-title":"Clinical analysis of Mycobacterium tuberculosis infection in patients with acquired immunodeficiency syndrome","volume":"32","author":"Chiu CP","year":"1999","unstructured":"Chiu CP, Wong WW, Kuo B, Tiao TM, Fung CP, Liu CY. 1999. 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