HIV-1 and <i>Chlamydia trachomatis</i> limit their respective growth but promote their survival in co-infected human macrophages

ABSTRACT HIV-1 and Chlamydia trachomatis (CT) are two significant sexually transmitted pathogens that frequently co-infect individuals. However, the mechanisms by which these two obligate intracellular pathogens interact at the cellular level remain elusive, particularly in macrophages, where persistent infections can occur. In this study, we demonstrate that CT generates inclusions in macrophages of murine and human origins. We also show that both HIV-1 and CT reciprocally reduce the growth and replication of each other within co-infected human macrophages, irrespective of whether the viral or bacterial infection is established first. Notably, the co-infection resulted in improved survival of the macrophage hosts as the inflammatory cell death pathways induced by CT were prevented by the virus. Collectively, these findings demonstrate that HIV-1 and CT can collaborate to persist in human macrophages. IMPORTANCE While HIV-1 and Chlamydia trachomatis (CT) infections are associated at the epidemiological level, very little is known at the cellular and molecular level about co-infections by these two intracellular pathogens. The significance of our research is in dissecting the impact of one pathogen on replication and production of infectious progeny by the other. For this, we studied human macrophages, which are targeted by both HIV-1 and CT and could play an important role in their intracellular persistence, using in vitro differentiated macrophages. This work reveals the close interplay between these two pathogens that benefit from each other to survive in human macrophages. Consequently, we emphasize the need to address these cells as a unique target during the co-infections.