EXPOSURE TO BACTERIAL PRODUCTS RENDERS MACROPHAGES HIGHLY SUSCEPTIBLETO T-TROPIC HIV-1

Microbial coinfections variably influence HIV-1 infection through immu ne activation or direct interaction of microorganisms with HIV-1 or it s target cells. In this study, we investigated whether exposure of mac rophages to bacterial products impacts the susceptibility of these cel ls to HIV-1 of different cellular tropisms. We demonstrate that (1) ma crophages exposed to bacterial cell wall components such as lipopolysa ccharide (LPS) (Gram-negative rods), lipoteichoic acid (Gram-positive cocci), and lipoarabinomannan (Mycobacteria) become highly susceptible to T cell (T)-tropic HIV-1 (which otherwise poorly replicate in macro phages) and variably susceptible to macrophage (M)-tropic HIV-1; (2) L PS-stimulated macrophages secrete a number of soluble factors (i.e., c hemokines, interferon, and proinflammatory cytokines) that variably af fect HIV infection of macrophages, depending on the virus phenotype in question; and (3) LPS-stimulated macrophages express CCR5 (a major co receptor for M-tropic HIV-1) at lower levels and CXCR4 (a major corece ptor for T-tropic HIV-1) at higher levels compared with unstimulated m acrophages. We hypothesize that a more favorable environment for T-tro pic HIV-1 and a less favorable or even unfavorable environment for M-t ropic HIV-1 secondary to exposure of macrophages to those bacterial pr oducts may accerelate a transition from M- to T-tropic viral phenotype , which is indicative of disease progression.