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A complication of TNF blockade therapy, which is used increasingly for the treatment of chronic inflammatory diseases, is the reactivation of latent tuberculosis. This study used a low-dose aerogenic model of murine tuberculosis to analyze the effect of TNF neutralization on disease progression in mice with chronic tuberculous infections. Histological, immunohistochemical, and flow cytometric analyses of<jats:italic>Mycobacterium tuberculosis<\/jats:italic>-infected lung tissues revealed that the neutralization of TNF results in marked disorganization of the tuberculous granuloma, as demonstrated by the dissolution of the previously described B-cell-macrophage unit in granulomatous tissues as well as by increased inflammatory cell infiltration. Quantitative gene expression studies using laser capture microdissected granulomatous lung tissues revealed that TNF blockade in mice chronically infected with<jats:italic>M. tuberculosis<\/jats:italic>leads to the enhanced expression of specific proinflammatory molecules. Collectively, these studies have provided evidence suggesting that in the chronic phase of<jats:italic>M. tuberculosis<\/jats:italic>infection, TNF is essential for maintaining the structure of the tuberculous granuloma and may regulate the granulomatous response by exerting an anti-inflammatory effect through modulation of the expression of proinflammatory mediators.<\/jats:p>","DOI":"10.1128\/iai.01011-07","type":"journal-article","created":{"date-parts":[[2008,1,23]],"date-time":"2008-01-23T01:44:47Z","timestamp":1201052687000},"page":"916-926","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":109,"title":["Tumor Necrosis Factor Blockade in Chronic Murine Tuberculosis Enhances Granulomatous Inflammation and Disorganizes Granulomas in the Lungs"],"prefix":"10.1128","volume":"76","author":[{"given":"Soumya D.","family":"Chakravarty","sequence":"first","affiliation":[{"name":"Departments of Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guofeng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming C.","family":"Tsai","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vellore P.","family":"Mohan","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology"},{"name":"Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simeone","family":"Marino","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan 48909"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise E.","family":"Kirschner","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan 48909"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luqi","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China 100700"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnne","family":"Flynn","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Biochemistry and Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Chan","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology"},{"name":"Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(03)00054-6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/429994"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.11.6846"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1786"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.174.6.1549"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.1.15"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.3.1723"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.175.4.1111"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.9.1573"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.3109\/07853899509002465"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1330"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.93"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90001-2"},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.4049\/jimmunol.160.4.1796","volume":"160","year":"1998","unstructured":"Flynn, J. 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