HIV-1 alters pathology and bacterial dissemination of Mycobacterium tuberculosis in co-infected humanized mice (MPF1P.765)

Abstract

Abstract Over a third of the world’s population is infected with Mycobacterium tuberculosis (M.tb). HIV infection significantly increases risk for M.tb infection and reactivation and TB is the most common cause of death among people with HIV. We have developed a humanized mouse model of HIV-1/M.tb co-infection as an investigative tool to study co-infection biology. Humanized mice were infected intravenously with a macrophage-tropic strain of HIV-1 (JR-CSF) or mock (BSA), and 3 weeks later were infected intranasally with M.tb (H37Rv). Animals became productively infected with HIV-1, as confirmed by serum ELISA for HIV-1 p24 capsid protein and detection of viral RNA by using qPCR. We further observed that HIV infected cells were localized to sites of inflammation and bacterial replication in the lung of HIV-1/M.tb co-infected animals as determined by immunohistochemistry staining for p24. The number of CD4+T cells in peripheral blood did not differ among M.tb- and M.tb/HIV-1-infected groups, indicating that the immune impairments due to HIV-1 were independent of peripheral T cell loss at this stage of co-infection. Consistent with clinical observations in co-infected human patients, greater mycobacterial dissemination was observed in M.tb/HIV-1 co-infected mice compared animals infected with M.tb only. These results suggest promise for use of the humanized mouse as a model to understand co-infection pathobiology and as a translational tool to develop vaccines and therapies.