Interaction ofMycobacterium aviumwith Human Monocyte-Derived Dendritic Cells

Abstract
The mechanism by which mycobacteria elicit class I-restricted T-cell responses remains undefined because these organisms have been shown to reside exclusively within membrane-bound vesicles in macrophages (Mφ), their primary host cells. We studied the interaction ofM. aviumwith dendritic cells (DC) because they are the most potent antigen-presenting cells and are abundant atM. aviuminfection sites. We observed that both DC and Mφ, generated from human peripheral blood monocytes by short-term culture, internalizedM. avium. The onset of programmed cell death and the percentage of apoptotic cells in infected DC and Mφ were comparable. However, following infection, DC secreted significantly larger amounts of interleukin-12, but not interleukin-1β, than infected autologous Mφ. Further analysis of infected cells showed that while phagosomes failed to acidify in bothM. avium-infected DC and Mφ, bacilli grew more slowly in DC. Electron microscopy studies revealed thatM. aviumresided within endocytic vacuoles in both cell types. The vacuolar membrane surrounding some bacilli in approximately 10% of the vacuoles in DC possessed several breaks. The importance of this finding will have to be addressed in future studies.