Establishment of a humanized mouse model for the study of co-infection with Human immunodeficiency virus (HIV) and Mycobacterium tuberculosis

Abstract Tuberculosis (TB), caused by Mycobacterium Tuberculosis (Mtb), continues to be one of the most important public health threats worldwide, being the second deadliest infectious disease, after COVID-19. The human immunodeficiency virus (HIV) is another equally important global public health issue. Co-infection with HIV and Mtb has severe effects in the host, with people living with HIV being 15-21 times more likely to develop active TB. The use of an appropriate animal model for HIV/Mtb co-infection that can recapitulate the diversity of the immune response in humans would be a very useful tool for basic and applied research. The present study aimed to develop a humanized mouse model for the study of HIV-Mtb coinfection. Using NSG-SGM3 mice that can engraft human stem cells, our results showed that these mice differentiated a full-lineage of human immune cell subsets. After co-infection with HIV and Mtb, the humanized mice showed decreased CD4+ T cell counts overtime with elevated HIV-1 load in sera, similar to the infection pattern in humans. Additionally, Mtb also caused infections in lungs and spleen, and induced the development of lesions in the lungs, detected by CT scan and histopathology. Distinct metabolomic profiles were observed in the different mice groups after infection. Our results suggest the capacity of this mouse model to recapitulate the effects of HIV and Mtb infections/co-infection, in the human host at a pathogenic, immunologic and metabolic level