CYTOTOXICITY FOR LUNG EPITHELIAL-CELLS IS A VIRULENCE-ASSOCIATED PHENOTYPE OF MYCOBACTERIUM-TUBERCULOSIS

Dissemination of viable tubercle bacilli from the Lung is a critical e vent in the establishment of Mycobacterium tuberculosis infection. We examined the possibility that M. tuberculosis bacteria could infect an d damage lung epithelial cells to determine whether direct penetration of the alveolar epithelium is a plausible route of M. tuberculosis in fection. While both virulent H37Rv tubercle bacilli and the attenuated Mycobacterium bovis BCG vaccine strain were able to enter A549 human lung epithelial cells in culture, only the virulent tubercle bacilli w ere cytotoxic for both polarized and nonpolarized epithelial monolayer s and macrophages, In addition, bacterial entry into epithelial cells, but not macrophages, was increased by intracellular passage through m acrophages, suggesting enhancement of a bacterially mediated cell entr y mechanism in bacteria grown within macrophages, These findings sugge st that RI, tuberculosis bacteria might have the ability to gain acces s to the host lymphatics and circulatory system by directly penetratin g the alveolar epithelial lining of an infected lung.