Topic Overview:
Tuberculosis (TB) is an infectious disease of global magnitude that kills more than 2 million people each year. Control of TB has been hampered by long and complex antibiotic regimens, the advent of antibiotic-resistant strains, and inconsistent efficacy of the only available vaccine, Mycobacterium bovis Bacille Calmette Guerin. Furthermore, M. tuberculosis latently infects one third of the world’s population, of which 10 percent (approximately 200 million people) will develop active TB during their lifetime. A critical need exists for improved TB treatment and vaccine strategies, but a much clearer understanding of the immunology of TB is required.

T-helper cells play a central role in orchestrating effective host responses against microbial pathogens and are classified as T-helper1 (Th1), T-helper 2 (Th2), and T-helper 17 (Th17) cell subsets. It is thought that Th1 cells producing the cytokine interferon gamma (IFNγ) are the primary effector cells required for control of intracellular pathogens such as M. tuberculosis; however, attempts in the last decade to improve Th1 cellular responses have not led to major advancements in TB vaccine strategies. Khader has demonstrated that production of another cytokine, interleukin 17 (IL-17), by Th17 cells influences both the generation and recruitment of protective, vaccine-induced Th1 cells to the lungs for control of M. tuberculosis.  Her work has shown that T-helper subset pathways are not “either-or” pathways but, rather, that they interact with and regulate each other.

Khader hopes to identify factors that can improve vaccine-induced T-cell responses and to incorporate these factors into the design of novel vaccine strategies against TB. Her lab has found that altering adjuvants and vaccine routes to promote IL-17 responses leads to better protection than existing TB vaccines, thereby highlighting IL-17 as a potential biomarker in rational TB vaccine development. Since several pulmonary pathogens, such as Francisella tularensis, Streptococcus pneumonia, Bordetella pertusis, and Pseudomonas aeruginosa, require IL-17 for vaccine-induced immunity,  Khader’s findings have broad implications for vaccine development against a wide variety of pulmonary infectious diseases.