Polybacterial challenge enhances HIV reactivation in latently infected macrophages and dendritic cells

A polymicrobial infection comprising subgingival biofilms is the trigger for the chronic immunoinflammatory lesions of periodontitis. These microbial biofilms interface with host immune cells that increase with progressing disease and could result in HIV reactivation in HIV-1-infected patients. Previous reports have focused on the ability of monospecies challenge of macrophages and dendritic cells to detail molecular aspects of their detection and signalling pathways. This study provides a seminal description of the responses of macrophages and dendritic cells to a polybacterial challenge using various oral bacteria as prototype stimuli to examine these response characteristics. The investigation employed a model of HIV-promoter activation and reactivation of HIV viral replication. Oral Gram-negative bacteria elicited significantly greater levels of HIV promoter activation and viral replication from all cell types, compared with Gram-positive bacteria. Selected combinations of oral Gram-negative bacteria elicited synergistic HIV promoter activation and viral replication in macrophages and immature dendritic cells. In mature dendritic cells, there was no synergism in HIV promoter activation and viral replication. Gram-positive bacteria showed no synergism in any cell model. These findings support the importance of determining the characteristics and impact of polybacterial challenges on immune cells to clarify the potential immune recognition and antigen processing that can occur in the oral cavity.