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Title: Two roads diverge in the lung: Host cell interactions with mycobacteria
Authors: Teitelbaum, Rachel
Keywords: Microbiology.
Cellular biology.
Issue Date: 1998
Publisher: ProQuest Dissertations & Theses
Citation: Source: Dissertation Abstracts International, Volume: 59-06, Section: B, page: 2573.;Advisors: Barry R. Bloom.
Abstract: Early events in mycobacterial interactions with host cells significantly affect pathogenesis, and the developing immune responses. Mycobacterium tuberculosis is thought to invade the host through alveolar macrophages. Mucosal M cells, associated with intraepithelial lymphoid compartments, may encounter M. tuberculosis, as well, prior to bacillary access of the alveolus. Our hypothesis was that M. tuberculosis enters M cells. Mice challenged intratracheally, demonstrated bacilli within M cells 3 hours post infection, by electron microscopy. Lymph nodes plated post-infection revealed that mucosal transcytosis facilitated seeding of the hilar nodes at 4 hours while bronchopulmonary nodes were not found to harbor bacilli at this time, implying an earlier, alveolar macrophage independent trafficking pathway. Osteopetrotic mice, deficient in M-CSF, demonstrated enhanced susceptibility to M. tuberculosis. These mice were shown to have a diminished capability of transporting bacilli from the mucosa to the intraepithelial lymphoid compartment, and ultimately to the lymph nodes, perhaps reflected in their enhanced susceptibility to infection.;Activated macrophages and cytotoxic T. lymphocytes (CTL) can be mycobactericidal. It is unclear how membrane-bound M. tb within the macrophage can access the class I pathway, for presentation to CTL. We demonstrate a size-restricted phagosomal permeability in macrophages early after infection utilizing tagged mycobacteria. Macrophages intracytoplasmically microinjected with tagged, sized dextrans demonstrated dextran colocalization with live, but not killed, mycobacteria, by confocal microscopy. Cytoplasmically located proteins access the phagosome, concurrent with mycobacterial antigen availability to the MHC class I presentation pathway. Taken together, these observations reveal new avenues of pursuit in host immune mechanisms in mycobacterial infection.
Appears in Collections:Albert Einstein College of Medicine: Doctoral Dissertations

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