Mycobacterium tuberculosis and Dendritic Cells: Who's Manipulating Whom?

Tuberculosis (TB) remains one of the most common potentially fatal infectious diseases worldwide. The need for more effective vaccines will benefit from a better understanding of the complex interactions between Mycobacterium tuberculosis and the human immune system. Among antigen-presenting cells, dendritic cells (DCs) are thought to play a central role in immunity against this bacillus, and numerous reports published since the early 1990s have focused on this topic. The culmination of the most appealing of these reports suggests the possible ability of M. tuberculosis to manipulate DCs to promote its own survival. These views, however, are rather difficult to reconcile with previous studies demonstrating the ability of mycobacteria-infected DCs to stimulate T lymphocytes in vitro and in vivo, and to confer significant protection against TB, as illustrated in murine models. The immune response elicited in the majority (>90%) of infected individuals, though not entirely perfect, is effective enough to allow the peaceful co-existence of the host and the microbe. A more vigorous response might prove sterilizing, but might also prove detrimental to the host tissues by inducing immunopathological injuries. Limiting DC functions to a certain extent may therefore be advantageous for the human host population as a whole, regardless of the 5-10% of infected individuals who will still develop the disease. The underlying question seems to be then: who's manipulating whom?