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

Michela Sali, Massimiliano Papi, Marco De Spirito, Giovanni Delogu, E Greco, Mb Santucci, Fr De Angelis, V Colizzi, M. Fraziano

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

29 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)125-132
Numero di pagine8
RivistaImmunology
Volume129
DOI
Stato di pubblicazionePubblicato - 2010

Keywords

  • Apoptosis
  • Cell Line
  • Cytoprotection
  • Disease Transmission, Infectious
  • Epithelial Cells
  • Host-Pathogen Interactions
  • Humans
  • Lysophospholipids
  • Macrophages, Alveolar
  • Mycobacterium tuberculosis
  • Phagosomes
  • Phospholipase D
  • Pulmonary Alveoli
  • Sphingosine
  • Tuberculosis

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