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Phagocyte -pathogen interactions
Among the various pathogens, their interactions with phagocytes display common themes as well as unique features. A thorough study of host factors involved in these interactions will not only deepen our understanding of pathogenesis, but also provide insight into fundamental aspects of eukaryotic cell biology. We used Legionella pneumophila, the bacteria causing Legionnaires' disease, as a model microorganism to dissect the host factors involved in parasitizing macrophages and environmental phagocytes such as amoebae. We characterized a murine alveolar macrophage cell line, MH-S, as a suitable in vitro model for Legionella. MH-S cells display similar characteristics to human primary macrophages during the intracellular replication and trafficking of L. pneumophila. Comparison of phagocytosis of L. pneumophila and latex beads by seven macrophage cell lines suggest that U-937 and THP-1 posses differences that are specific to phagocytosis of L. pneumophila. We investigated the role of integrin α6, a highly expressed surface molecule in U-937, as a potential receptor for Legionella. Antibody blocking and RNA interference studies suggest that integrin α6 plays a role during interactions of L. pneumophila with macrophages and epithelial cells. The interactions of Legionella with environmental protozoa, such as Acanthamoeba castellanii, share similarities with that of macrophages. We isolated four A. castellanii variants using Legionella cytocidal activity as a selection. These variants display reduced phagocytosis of bacteria, enhanced bacterial killing as well as increased lysosome fusion with bacterial phagosomes. Proteomic studies demonstrated that hsp90 protein levels are reduced in the variants. Inhibition of hsp90 reduces phagocytosis and intracellular replication of Legionella in macrophages, suggesting that hsp90 plays an important role in phagocytosis and intracellular replication of Legionella. Thus, these studies have resulted in the development of improved host virulence models as well as an enhanced understanding of host-pathogen interactions. ^
Yan, Ling, "Phagocyte -pathogen interactions" (2004). ETD collection for University of Nebraska - Lincoln. AAI3137865.