Mycobacterial lysocardiolipin is exported from phagosomes upon cleavage ofcardiolipin by a macrophage-derived lysosomal phospholipase A(2)

Pathogenic mycobacteria are able to survive and proliferate in phagosomes w ithin host macrophages (M phi). This capability has been attributed in part to their cell wall, which consists of various unique lipids. Some of these are important in the host-pathogen interaction, such as resistance against microbicidal effector mechanisms and modulation of host cell functions, an d/or are presented as Ags to T cells. Here we show that two lipids are rele ased from the mycobacterial cell wall within the phagosome of infected M ph i and transported out of this compartment into intracellular vesicles. One of these lipids was identified as lysocardiolipin. Lysocardiolipin was gene rated through cleavage of mycobacterial cardiolipin by a Ca2+ -independent phospholipase A(2) present in M phi lysosomes. This result indicates that l ysosomal host cell enzymes can interact with released mycobacterial lipids to generate new products with a different intracellular distribution. This represents a novel pathway for the modification of bacterial lipid Ags.