Janus -faced liposomes enhance antimicrobial innate immune response in Mycobacterium tuberculosis infection
We have generated unique asymmetric liposomes with phosphatidylserine (PS) distributed at the outer membrane surface to resemble apoptotic bodies and phosphatidic acid (PA) at the inner layer as a strategy to enhance innate antimycobacterial activity in phagocytes while limiting the inflammatory response. Results show that these apoptotic body-like liposomes carrying PA (ABL/PA) ( i ) are more efficiently internalized by human macrophages than by nonprofessional phagocytes, ( ii ) induce cytosolic Ca 2+ influx, ( iii ) promote Ca 2+ -dependent maturation of phagolysosomes containing Mycobacterium tuberculosis (MTB), ( iv ) induce Ca 2+ -dependent reactive oxygen species (ROS) production, (…
Phosphatidylserine liposomes reduce inflammatory response, mycobacterial viability and HIV replication in coinfected human macrophages
AbstractChronic immune activation is the key pathogenetic event of Mycobacterium tuberculosis-human immunodeficiency virus (HIV) coinfection. We assessed the therapeutic value of phosphatidylserine-liposome (PS-L) in an in vitro model of M. tuberculosis-HIV coinfection. PS-L reduced nuclear factor-κB activation and the downstream production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in bacille Calmette-Guérin-infected macrophages and of TNF-α and IL-1β in M. tuberculosis-infected and M. tuberculosis-HIV–coinfected macrophages. Importantly, a significant reduction of intracellular M. tuberculosis viability and HIV replication were also observed. These results suppor…