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

Emanuela Greco, Marilina B. Santucci, Michela Sali, Francesca R. De Angelis, Massimiliano Papi, Marco De Spirito, Giovanni Delogu, Vittorio Colizzi, Maurizio Fraziano

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)125-132
Number of pages8
JournalImmunology
Volume129
Issue number1
DOIs
Publication statusPublished - Jan 2010

Keywords

  • Alveolar epithelial cells
  • Dissemination
  • Lysophospholipid
  • Primary infection
  • Tuberculosis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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