Internalization of Mycobacterium tuberculosis by macropinocytosis in non-phagocytic cells

Mycobacterium tuberculosis (MTB) is an intracellular pathogen that initially invades the alveolar macrophages of infected individuals. MTB is also known to invade respiratory epithelial cells. To understand the mechanism of epithelial invasion, we investigated the interaction of MTB (H37Rv strain) with non-phagocytic type-II (A549) human pneumocytes. The internalization of the organism was analyzed through optical, fluorescent and electron (transmission and scanning) microscopy. Infection of A549 cells with MTB showed intracellular multiplication of the organism. Microscopy revealed the formation of membrane ruffles totally or partially surrounding the surface adherent mycobacteria. Fluorescent microscopy showed that MTB induced changes in the distribution of actin filaments. Since heat killed MTB failed to induce actin mobilization, perhaps, internalization process is mediated by the soluble products of the metabolically active mycobacterium. Overall, these findings suggest that internalization of MTB by non-phagocytic cells might be through a macropinocytosis or induced-phagocytosis processes, and possibly some bacterial secretory product is responsible for triggering this phenomenon. (C) 2003 Elsevier Ltd. All rights reserved.