Investigating the role of the pulmonary innate immune system in anti-tuberculosis immunity

Abstract

M.tb, the causative agent of pulmonary tuberculosis (TB) remains one of the leading causes of infectious disease-based death worldwide. BCG, the only clinically approved TB vaccine, has been in use for almost a century to vaccinate against TB. Despite its success in protecting against disseminated forms of TB, it is unable to provide protection against pulmonary M.tb infection. Although there have been many recent efforts to enhance or replace BCG, our lack of understanding towards host immunity against M.tb has substantially hindered this goal. One aspect of pulmonary M.tb infection that remains poorly understood is the induction of Th1 immunity, which is substantially delayed in comparison to other pulmonary infections. This allows the bacteria to establish an infectious foothold within the host and impairs the ability of the host to clear the infection. Given the importance of the innate immune response in the induction of adaptive immunity, this delay in the establishment of Th1 immunity following pulmonary M.tb infection is likely due to a defect in the early innate immune response. However, the specific roles of this immune compartment in regards to T cell activation following pulmonary M.tb infection is still not well understood. As such, the scope of this thesis is to gain an increased understanding towards the role of the innate immune compartment in the generation of Th1 responses. Such insights will allow us to develop new strategies to improve upon future and existing TB vaccine design.