Dual mechanism for  Mycobacterium tuberculosis  cytotoxicity on lung epithelial cells.
Mycobacterium tuberculosis  strains CDC1551 and Erdman were used to assess cytotoxicity in infected A549 human alveolar epithelial cell monolayers. Strain CDC1551 was found to induce qualitatively greater disruption of A549 monolayers than was strain Erdman, although total intracellular and cell-associated bacterial growth rates over the course of the infections were not significantly different. Cell-free culture supernatants from human monocytic cells infected with either of the 2 M. tuberculosis strains produced a cytotoxic effect on A549 cells, correlating with the amount of tumor necrosis factor alpha (TNF-α) released by the infected monocytes. The addition of TNF-α-neutralizing antibodies to the supernatants from infected monocyte cultures did prevent the induction of a cytotoxic effect on A549 cells overlaid with this mixture but did not prevent the death of epithelial cells when added prior to infection with M. tuberculosis bacilli. Thus, these data agree with previous observations that lung epithelial cells infected with M. tuberculosis bacilli are rapidly killed in vitro. In addition, the data indicate that some of the observed epithelial cell killing may be collateral damage; the result of TNF-α released from M. tuberculosis-infected monocytes.
Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey, Mexico. jorge.castro@biomedicas.net
Jorge
J
Castro-Garza
W Edward
WE
Swords
Russell K
RK
Karls
Frederick D
FD
Quinn
D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000633:toxicity; D003601:Cytotoxicity Tests, Immunologic; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D009000:Monocytes / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000378:metabolism*; D014376:Tuberculosis / Q000382:microbiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D057134:Antibodies, Neutralizing; D017077:Culture Media, Conditioned; D014409:Tumor Necrosis Factor-alpha