Pulmonary Tuberculosis in Humanized Mice Infected with HIV-1

Rebecca J. Nusbaum, Veronica E. Calderon, Matthew B. Huante, Putri Sutjita, Sudhamathi Vijayakumar, Katrina L. Lancaster, Robert L. Hunter, Jeffrey K. Actor, Jeffrey D. Cirillo, Judith Aronson, Benjamin B. Gelman, Joshua G. Lisinicchia, Gustavo Valbuena, Janice J. Endsley

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Co-infection with HIV increases the morbidity and mortality associated with tuberculosis due to multiple factors including a poorly understood microbial synergy. We developed a novel small animal model of co-infection in the humanized mouse to investigate how HIV infection disrupts pulmonary containment of Mtb. Following dual infection, HIV-infected cells were localized to sites of Mtb-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-1β, IL-6, TNFα, and IL-8), neutrophil accumulation, and greater lung pathology in the Mtb-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 Mtb, leading to poorly formed granulomas, more severe lung pathology, and increased mycobacterial burden and dissemination.

Original languageEnglish (US)
Article number21522
JournalScientific reports
Volume6
DOIs
StatePublished - Feb 24 2016

ASJC Scopus subject areas

  • General

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