Khader Lab Research

Tuberculosis (TB) kills more than 2 million people worldwide every year. The widely used TB vaccine, Bacille Calmette Guerin (BCG) has variable efficacy and has prompted the search for more effective vaccines. Although significant progress has been made in identifying protective Mycobacterium tuberculosis (Mtb) antigen candidates, our poor understanding of how immune responses mediate protection in the lung remains a major hurdle to successful vaccine design. 

The major goal of my lab is to define the basic requirements for induction of protective immunity in the lung against pulmonary pathogens such as Mtb. Our past work has described a novel role for the cytokine Interleukin-17 (IL-17) in vaccine-induced immunity against tuberculosis. More recent work from my lab has utilized this information to target and boost lung Th17 responses to improve vaccine-induced immunity against tuberculosis. We have identified that mucosal immunization with Mtb antigen induces a population of lung-resident Th17 cells. IL-17 made by Th17 cells mediate protection in the host by inducing formation of lymphoid follicles in the lung to initiate T cell localization near infected macrophage  for Mtb control. In contrast, IL-17 is a potent proinflammatory cytokine and expression of this cytokine during TB is associated with induction of neutrophil accumulation and associated lung pathology. Thus, current approaches in the Khader lab are focused on improving lung Th17 responses to improve vaccine strategies for TB, without inducing the pathological effects of IL-17 mediated lung inflammation. These approaches revolve around use of alternative routes of immunization, use of novel Th17 adjuvants, and altering the location of Th17 cells in the lung as new ways to boost vaccine-induced immunity against TB.