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Abstract
One goal of infectious disease research is to determine points of intervention which will alter the scales of infection in favor of the host. To accomplish this goal, it is crucial to have a thorough understanding of the dynamic pathogen/host interplay which results in observed pathology. Until recently, studies of pathogenic Mycobacterium species responsible for pulmonary infections focused on the interaction of these bacteria with macrophages leaving the role for other host cell populations present in the lung unexplored. This body of work employs various techniques to examine trafficking of Mycobacterium tuberculosis (Mtb) bacilli in human alveolar type II pneumocytes from initial interactions at the host cell plasma membrane, internalization and passage through the fluid phagosomal/autophagosomal pathway. Data suggest that Mtb infection of epithelial cells is characterized by aggregation of large cholesterol-dense regions, or lipid rafts, which result in bacilli engulfment. Inhibition of raft formation significantly impacts early infection resulting in decreased numbers of internalized bacteria and diminished survivability of those bacilli within 24 hours of infection. Once internalized the Mtb bacilli traffic through a phagosomal/autophagosomal pathway. Interference with the autophagosomal pathway results in decreased numbers of virulent Mtb bacteria and increased host cell survival. Taken together these data strongly suggest that Mtb has the ability to alter the epithelial cell autophagy pathway to support infection by the bacterium. The data presented here describe Mtb-induced changes in the host cell plasma membrane which facilitate infection success, as well as the trafficking route for virulent Mtb bacilli that differs from what has been previously described in macrophages. As with some other bacterial pathogens, it is evident that M. tuberculosis employs numerous strategies for survival and replication which are unique to the particular host cell infected.