Interaction of Mycobacterium avium with human monocyte-derived dendritic cells

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 (M phi), their primary host cells. We studied the interaction of M. avium with dendritic cells (DC) because they are the most potent antigen-presenting cells and are abundant at M. avium infection sites. We observed that both DC and M phi, generated from human peripheral blood monocytes by short-term culture, internalized ICI. avium. The onset of programmed cell death and the percentage of apoptotic cells in infected DC and M phi, were comparable. However, following infection, DC secreted significantly larger amounts of interleukin-12, but not interleukin-1 beta, than infected autologous M phi. Further analysis of infected cells showed that while phagosomes failed to acidify in both M, avium-infected DC and M phi, bacilli grew more slowly in DC. Electron microscopy studies revealed that M. avium resided 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.