{"id":4575,"date":"2021-02-05T12:55:04","date_gmt":"2021-02-05T17:55:04","guid":{"rendered":"https:\/\/www.bumc.bu.edu\/pulmonary\/?p=4575"},"modified":"2021-02-05T12:55:04","modified_gmt":"2021-02-05T17:55:04","slug":"new-ways-to-attack-necrotic-tuberculous-granulomas-in-the-lung","status":"publish","type":"post","link":"https:\/\/www.bumc.bu.edu\/pulmonary\/2021\/02\/05\/new-ways-to-attack-necrotic-tuberculous-granulomas-in-the-lung\/","title":{"rendered":"New ways to attack necrotic tuberculous granulomas in the lung"},"content":{"rendered":"

\"\"Approximately one quarter of all humans have been infected during their lifetime with Mycobacterium tuberculosis – the bacteria that causes tuberculosis (TB). Most of the infected people control the bacteria that remain dormant for many years. In some individuals, however, the bacteria grow in the lungs, causing severe lung damage, including the formation of necrosis and cavities. Those lung lesions become fertile ground for the bacterial growth\u202fand spread from human to human via aerosols. The mechanism by which only some humans infected with\u202fMycobacterium tuberculosis\u202fdevelop progressive lung disease while others form\u202fgranulomas that control\u202fthe infection,\u202fremains poorly defined.<\/p>\n

Dr. Kramnik’s laboratory has developed a unique mouse model that forms\u202fchronic necrotic lung lesions, similar to human TB granulomas. In these mice, TB susceptibility is linked to dysfunction of immune cells that normally harbor and control the bacteria \u2013 macrophages. \u202fWhen activated, the mutant macrophages develop unresolving stress that\u202fweakens their ability to fight the bacteria. In this newly published paper, Bhattacharya et al\u202fdissected\u202fthe mechanism of the escalating\u202fstress and linked it to the hyperactivity of the type I interferon pathway. Remarkably, this pathway is involved in the control of viral infections but\u202fis also\u202faberrantly activated in human TB patients. The authors found that interrupting the vicious cycle of the interferon-driven\u202fstress response in macrophages using small molecule inhibitor ISRIB reduced inflammation and damage in the lungs of MTB-infected mice. This study demonstrates that\u202fthe unresolving\u202fstress\u202fplays a causal role in the progression of TB lung lesions towards necrosis. Correction\u202fof the aberrant stress response with inhibitors may offer a novel\u202ftherapeutic strategy\u202fthat will allow shortening TB treatment and reducing the pathogen transmission.<\/p>\n

Bhattacharya, B, S Xiao, S Chatterjee, M Urbanowski, A Ordonez, EA Ihms,\u00a0G Agrahari, S Lun, R Berland, A Pichugin, Y Gao, J Connor, AR Ivanov, B Yan, L Kobzik, B Koo, S Jain, W Bishai, I Kramnik. 2021. The integrated stress response mediates necrosis in murine Mycobacterium tuberculosis granulomas. J Clin Invest<\/em> 131: 369\u201315<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"

Approximately one quarter of all humans have been infected during their lifetime with Mycobacterium tuberculosis – the bacteria that causes tuberculosis (TB). Most of the infected people control the bacteria that remain dormant for many years. In some individuals, however, the bacteria grow in the lungs, causing severe lung damage, including the formation of necrosis […]<\/p>\n","protected":false},"author":16527,"featured_media":4577,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[6012],"tags":[],"_links":{"self":[{"href":"https:\/\/www.bumc.bu.edu\/pulmonary\/wp-json\/wp\/v2\/posts\/4575"}],"collection":[{"href":"https:\/\/www.bumc.bu.edu\/pulmonary\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bumc.bu.edu\/pulmonary\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/pulmonary\/wp-json\/wp\/v2\/users\/16527"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/pulmonary\/wp-json\/wp\/v2\/comments?post=4575"}],"version-history":[{"count":1,"href":"https:\/\/www.bumc.bu.edu\/pulmonary\/wp-json\/wp\/v2\/posts\/4575\/revisions"}],"predecessor-version":[{"id":4576,"href":"https:\/\/www.bumc.bu.edu\/pulmonary\/wp-json\/wp\/v2\/posts\/4575\/revisions\/4576"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/pulmonary\/wp-json\/wp\/v2\/media\/4577"}],"wp:attachment":[{"href":"https:\/\/www.bumc.bu.edu\/pulmonary\/wp-json\/wp\/v2\/media?parent=4575"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/pulmonary\/wp-json\/wp\/v2\/categories?post=4575"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/pulmonary\/wp-json\/wp\/v2\/tags?post=4575"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}