title: Mycobacterial lysocardiolipin is exported from phagosomes upon cleavage of cardiolipin by a macrophage-derived lysosomal phospholipase A2.
abstract: Pathogenic mycobacteria are able to survive and proliferate in phagosomes within host macrophages (Mphi). 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, and/or are presented as Ags to T cells. Here we show that two lipids are released from the mycobacterial cell wall within the phagosome of infected Mphi and transported out of this compartment into intracellular vesicles. One of these lipids was identified as lysocardiolipin. Lysocardiolipin was generated through cleavage of mycobacterial cardiolipin by a Ca2+-independent phospholipase A2 present in Mphi lysosomes. This result indicates that lysosomal 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.
authors.affiliation: Max-Planck Institute for Infection Biology, Department of Immunology, Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Fischer
authors.forename: D
authors.initials: D
authors.lastname: Chatterjee
authors.forename: J
authors.initials: J
authors.lastname: Torrelles
authors.forename: P J
authors.initials: PJ
authors.lastname: Brennan
authors.forename: S H
authors.initials: SH
authors.lastname: Kaufmann
authors.forename: U E
authors.initials: UE
authors.lastname: Schaible
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D002118:Calcium / Q000502:physiology; D002308:Cardiolipins / Q000378:metabolism*; D002478:Cells, Cultured; D003470:Culture Media / Q000378:metabolism; D054522:Group VI Phospholipases A2; D006868:Hydrolysis; D050356:Lipid Metabolism; D008247:Lysosomes / Q000201:enzymology* / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology* / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D009163:Mycobacterium bovis / Q000254:growth & development / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2
chemical_list: D002308:Cardiolipins; D003470:Culture Media; D010741:Phospholipases A; D054522:Group VI Phospholipases A2; D054467:Phospholipases A2; C516476:Pla2g6 protein, mouse; D002118:Calcium