title: Pulmonary Tuberculosis in Humanized Mice Infected with HIV-1.
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.
authors.affiliation: University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Nusbaum
authors.affiliation: University of Texas El Paso, El Paso, TX 79902, USA.
authors.forename: Veronica E
authors.initials: VE
authors.lastname: Calderon
authors.affiliation: University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Huante
authors.affiliation: University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Putri
authors.initials: P
authors.lastname: Sutjita
authors.affiliation: University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Sudhamathi
authors.initials: S
authors.lastname: Vijayakumar
authors.affiliation: University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Katrina L
authors.initials: KL
authors.lastname: Lancaster
authors.affiliation: University of Texas-Houston Health Science Center, Houston, TX 77030, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hunter
authors.affiliation: University of Texas-Houston Health Science Center, Houston, TX 77030, USA.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Actor
authors.affiliation: Texas A&M Health Sciences Center, College Station, TX 77853, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Cirillo
authors.affiliation: University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Aronson
authors.affiliation: University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Gelman
authors.affiliation: University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Joshua G
authors.initials: JG
authors.lastname: Lisinicchia
authors.affiliation: University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Valbuena
authors.affiliation: University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Janice J
authors.initials: JJ
authors.lastname: Endsley
mesh_terms: D000818:Animals; D060085:Coinfection / Q000276:immunology*; D004195:Disease Models, Animal; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D016867:Immunocompromised Host; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D020556:Neutrophil Infiltration; D014397:Tuberculosis, Pulmonary / Q000276:immunology*