title: Natural lysophospholipids reduce Mycobacterium tuberculosis-induced cytotoxicity and induce anti-mycobacterial activity by a phagolysosome maturation-dependent mechanism in A549 type II alveolar epithelial cells.
abstract: Human alveolar epithelial cells actively contribute to the innate immune response in the lung and play an important role in mycobacterial dissemination during primary infection, by undergoing cell death and by releasing mycobacteria. In the present study, we report that natural lysophospholipids, such as lysophosphatidic acid or sphingosine 1-phosphate, reduce Mycobacterium tuberculosis-induced cytotoxicity and enhance anti-mycobacterial activity in the A549 cell line, used as a model of type II alveolar epithelial cells. Intracellular mycobacterial killing was strictly dependent on phagolysosome maturation, which in turn was promoted by the activation of a Ca(2+)dependent phospholipase D. Finally, the restriction of mycobacteria in highly microbiocidal compartments was associated, in vitro, with a significant decrease in mycobacterial dissemination to macrophages. Taken as whole, these results suggest that the pulmonary lysophospholipid microenvironment may play a protective role during the early phases of host-pathogen interaction by enhancing anti-mycobacterial activity in type II alveolar epithelial cells.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Greco
authors.forename: Marilina B
authors.initials: MB
authors.lastname: Santucci
authors.forename: Michela
authors.initials: M
authors.lastname: Sali
authors.forename: Francesca R
authors.initials: FR
authors.lastname: De Angelis
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Papi
authors.forename: Marco
authors.initials: M
authors.lastname: De Spirito
authors.forename: Giovanni
authors.initials: G
authors.lastname: Delogu
authors.forename: Vittorio
authors.initials: V
authors.lastname: Colizzi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fraziano
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D019610:Cytoprotection; D018562:Disease Transmission, Infectious; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D054884:Host-Pathogen Interactions; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D010588:Phagosomes / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000473:pathology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014376:Tuberculosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D010739:Phospholipase D; D013110:Sphingosine; C032881:lysophosphatidic acid