Mycobacteria-infected bystander macrophages trigger maturation of dendritic cells and enhance their ability to mediate HIV transinfection

Abstract

Synergistic interplay between Mycobacterium tuberculosis (Mtb) and HIV in coinfected individuals leads to the acceleration of both tuberculosis and HIV disease. Mtb, as well as HIV, may modulate the function of many immune cells, including DCs. To dissect the bystander impact of Mφs infected with Mtb on DC functionality, we here investigated changes in DC phenotype, cytokine profiles, and HIV-1 transinfecting ability. An in vitro system was used in which human monocyte-derived DCs were exposed to soluble factors released by Mφs infected with mycobacteria, including virulent clinical Mtb isolates and nonvirulent BCG. Soluble factors secreted from Mtb-infected Mφs, and to a lesser extent BCG-infected Mφs, resulted in the production of proinflammatory cytokines and partial upregulation of DC maturation markers. Interestingly, the HIV-1 transinfecting ability of DCs was enhanced upon exposure to soluble factors released by Mtb-infected Mφs. In summary, our study shows that DCs exposed to soluble factors released by mycobacteria-infected Mφs undergo maturation and display an augmented ability to transmit HIV-1 in trans. These findings highlight the important role of bystander effects during the course of Mtb-HIV coinfection and suggest that Mtb-infected Mφs may contribute to an environment that supports DC-mediated spread and amplification of HIV in coinfected individuals.