Cheryl Day, PhD

ARTDTP Research Discipline:

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. The Day laboratory is currently performing human immunology studies with blood samples obtained from adults with latent M. tuberculosis infection and with pulmonary TB disease in Cape Town, South Africa. 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.. 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. This area is of special importance in the current era of multiple antibiotic resistance expressed by M. tuberculosis, which now threatens conventional drug therapy regimens. 

ARTDTP Faculty Collaborators:

Rafi Ahmed, PhD

Jyothi Rengarajan, PhD

Thomas M. Shinnick, PhD