Tuberculosis (TB) is still a common infectious disease in developing countries, but it is also re-emerging in industrialized nations due to the HIV/AIDS pandemic. In addition to bacillary virulence, the host immune response plays a major role in the development of an active disease (either as a primary infection or reactivation) and in controlling the infection.

Even though several mechanisms are involved in regulating the human immune response, biological environment seems to be determinant. In this context, the integrated neuro-immune-endocrine system strongly influences TB clinical outcome. One of the most important clinical aspects of TB is shown when the infection locates in the central nervous system (CNS), in which a very different set of immune responses is induced. Herein we review several aspects of the paradoxical immune response triggered during CNS-TB infection, and discuss the implications of this response in the cerebral infection outcome.