Inadequate Clearance of Translocated Bacterial Products in HIV-Infected Humanized Mice

Author Summary

HIV infection leads to continuous destruction of the body's immune defenses. Furthermore, disease progression is linked to heightened levels of immune activation. However, the underlying activating factors and their relationships to HIV pathogenesis are controversial. In patients with chronic HIV infection, bacteria and their products, such as lipopolysaccharide (LPS), translocate from the intestinal lumen into the systemic circulation. In the current study, we investigated the pathogenic potential of bacterial translocation in HIV-infected humanized mice. By modulating the amount of bacterial translocation in the mice, we determined that LPS elevation depends on intestinal barrier dysfunction and defective LPS clearance by macrophages. HIV-infected mice showed inadequate LPS clearance, leading to a cascade of uncontrolled bacterial translocation, T-cell activation, HIV replication, and T-cell loss. Our study highlights how important the interplay between different immune cells is for maintaining a healthy balance between immune activation with the goal to defend the body against microbes and detrimental activation that fuels HIV replication.