Optimization of inhaled therapies for tuberculosis: The role of macrophages and dendritic cells

Abstract

Inhaled therapies in the form of drugs or vaccines for tuberculosis treatment were reported about a decade ago. Experts around the world met to discuss the scientific progress in inhaled therapies at the international symposium ?Optimization of inhaled Tuberculosis therapies and implications for host?pathogen interactions? held in New Delhi, India on November 3?5, 2009. The meeting was organized by the Central Drug Research Institute (CDRI) Lucknow, India. The lung is the main route for infection with Mycobacterium tuberculosis bacilli and the primary site of reactivation of latent disease. The only available vaccine BCG is relatively ineffective at preventing tuberculosis disease and current therapy requires prolonged treatment with drugs which results in low patient compliance. Consequently, there is a need to design new vaccines and therapies for this disease. Recently there has been increased interest in the development of inhaled formulations to deliver anti-mycobacterial drugs and vaccines directly to the lung and many of these therapies are designed to target lung macrophages and dendritic cells. However, the development of effective inhaled therapies requires an understanding of the unique function and immunosuppressive environment of the lung which is driven, in part, by alveolar macrophages and dendritic cells. In this review, we will discuss the role of alveolar macrophages and dendritic cells in the host immune response to M. tuberculosis infection and the ways in which inhaled therapies might enhance the anti-microbial response of phagocytes and boost pulmonary immunity.