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We developed a novel small animal model of co-infection in the humanized mouse to investigate how HIV infection disrupts pulmonary containment of <jats:italic>Mtb<\/jats:italic>. Following dual infection, HIV-infected cells were localized to sites of <jats:italic>Mtb<\/jats:italic>-driven inflammation and mycobacterial replication in the lung. Consistent with disease in human subjects, we observed increased mycobacterial burden, loss of granuloma structure and increased progression of TB disease, due to HIV co-infection. Importantly, we observed an HIV-dependent pro-inflammatory cytokine signature (IL-1\u03b2, IL-6, TNF\u03b1 and IL-8), neutrophil accumulation and greater lung pathology in the <jats:italic>Mtb<\/jats:italic>-co-infected lung. These results suggest that in the early stages of acute co-infection in the humanized mouse, infection with HIV exacerbates the pro-inflammatory response to pulmonary <jats:italic>Mtb<\/jats:italic>, leading to poorly formed granulomas, more severe lung pathology and increased mycobacterial burden and dissemination.<\/jats:p>","DOI":"10.1038\/srep21522","type":"journal-article","created":{"date-parts":[[2016,2,24]],"date-time":"2016-02-24T10:27:23Z","timestamp":1456309643000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Pulmonary Tuberculosis in Humanized Mice Infected with HIV-1"],"prefix":"10.1038","volume":"6","author":[{"given":"Rebecca J.","family":"Nusbaum","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica E.","family":"Calderon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew B.","family":"Huante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Putri","family":"Sutjita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhamathi","family":"Vijayakumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina L.","family":"Lancaster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Hunter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey K.","family":"Actor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Cirillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Aronson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin B.","family":"Gelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua G.","family":"Lisinicchia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Valbuena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice J.","family":"Endsley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,2,24]]},"reference":[{"key":"BFsrep21522_CR1","unstructured":"Organization, W. 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