Unraveling the host immune response to vacuolar pathogens

Abstract

Intracellular respiratory pathogens, including Mycobacterium tuberculosis, Legionella pneumophila and Chlamydia pneumoniae, continue to cause much morbidity and mortality worldwide. These bacterial pathogens survive and multiply inside host cells in a non-degradative phagocytic vacuole that does not fuse with lysosomes, and are therefore known as vacuolar pathogens. In the lung, they grow primarily in alveolar macrophages and infection results in pneumonia. A better understanding of the mechanisms underlying the host immune responses to these pathogens is essential to develop more effective treatment and prevention strategies. In this context, pathogen-induced cytokines, their cellular sources and their regulation have been given more attention. The prototypical Th1 cytokine, IFN-γ, which is produced by NK- and T cells, has been recognized as the critical cytokine necessary to clear an infection associated with vacuolar pathogens. IFN-γ controls vacuolar pathogens through the generation of reactive oxygen intermediates (ROIs) and the production of reactive nitrogen intermediates (RNIs). In general, IFN-γ is induced by IL-12 as part of both the innate and adaptive immune responses.