A Novel Humanized Mouse Model for HIV and Tuberculosis Co-infection Studies

Abstract

ABSTRACTTuberculosis (TB), caused byMycobacterium tuberculosis(Mtb), continues to be a major public health problem worldwide. The human immunodeficiency virus (HIV) is another equally important life-threatening pathogen. Further, co-infections with HIV andMtbhave severe effects in the host, with people infected with HIV being fifteen to twenty-one times more likely to develop active TB. The use of an appropriate animal model for HIV/Mtbco-infection that can recapitulate the diversity of the immune response in humans would be a useful tool for conducting basic and translational research in HIV/Mtbinfections. The present study was focused on developing a humanized mouse model for investigations on HIV-Mtbco-infection. Using NSG-SGM3 mice that can engraft human stem cells, our studies showed that they were able to engraft human CD34+ stem cells which then differentiate into a full-lineage of human immune cell subsets. After co-infection with HIV andMtb, these mice showed decrease in CD4+ T cell counts overtime and elevated HIV load in the sera, similar to the infection pattern of humans. Additionally,Mtbcaused infections in both lungs and spleen, and induced the development of granulomatous lesions in the lungs, detected by CT scan and histopathology. Distinct metabolomic profiles were also observed in the tissues from different mouse groups after co-infections. Our results suggest that the humanized NSG-SGM3 mice are able to recapitulate the effects of HIV andMtbinfections and co-infection in the human host at pathological, immunological and metabolism levels, providing a dependable small animal model for studying HIV/Mtbco-infection.