Cheryl L. Day, PhD
Department of Microbiology & Immunology
Approximately 90% of immunocompetent individuals infected with Mycobacterium tuberculosis remain asymptomatic, thus providing compelling evidence that the host immune response is usually successful in containing the infection. However, the remaining 10% of infected individuals develop active tuberculosis (TB), although the precise mechanisms leading to this immunological failure and subsequent disease progression are not known. Those who are successfully treated for active TB remain susceptible to relapse and/or re-infection, thus strongly indicating generation of impaired effector and memory T cells in individuals with active TB disease. Moreover, co-infection with HIV, which impairs cellular immune responses, greatly increases the risk of development of active TB.
We are currently performing human immunology studies with blood samples from adults with latent M. tuberculosis infection and with pulmonary TB disease. Specific questions in TB cellular immunology currently being addressed include defining immunoregulatory pathways that may be dysregulated in individuals who develop active TB disease; determining the effect of mycobacterial antigen load on the functional capacity of M. tuberculosis-specific T cell responses; defining immunological parameters that are associated with successful immune control of M. tuberculosis infection; determining the role of CD8 T cells in control of M. tuberculosis replication; and determining the effect of anti-TB treatment on M. tuberculosis-specific memory T cell function. Furthermore, exciting novel studies are being initiated to characterize the role of natural killer (NK) cells and antibodies in M. tuberculosis infection and disease progression. Elucidating mechanisms contributing to immunological failure in persons who develop active TB disease will facilitate new avenues of research on immunotherapeutic interventions and the rational design of novel TB vaccines.