%0 Journal Article
%T Interferon-¦Ã Regulates the Death of M. tuberculosis-Infected Macrophages
%A Jinhee Lee
%A Hardy Kornfeld
%J Journal of Cell Death
%D 2010
%I 
%X We previously described a caspase-independent death induced in macrophages by a high intracellular burden of Mycobacterium tuberculosis (Mtb). This death, with features of apoptosis and necrosis, releases viable bacilli for spreading infection. Interferon (IFN)-¦Ã promotes survival of macrophages with a low intracellular Mtb load by inhibiting bacterial replication. Macrophages in na ve hosts are unable to restrict Mtb replication following aerosol transmission, but IFN-¦Ã is increasingly present when adaptive immunity is expressed in the lungs ¡«2 weeks post-infection. We therefore investigated the effects of IFN-¦Ã on macrophages challenged with Mtb at high multiplicity of infection (MOI). In contrast to the response at low MOI, IFN-¦Ã accelerated the death of heavily infected macrophages and altered the characteristics of the dying cells. IFN-¦Ã increased caspase-dependent DNA cleavage and apoptotic vesicle formation, but it also increased mitochondrial injury and release of LDH and HMGB1 in a caspase-independent manner. Adaptive immunity in tuberculosis (TB), mediated primarily by IFN-¦Ã, has differential effects on Mtb-induced macrophage cell death depending on the intracellular bacillary load. While IFN-¦Ã generally promotes host defense, our data suggest that its effects on heavily infected macrophages could also accelerate necrosis and spreading infection in TB disease.
%U http://la-press.com/interferon-gamma-regulates-the-death-of-m-tuberculosis-infected-macrop-a1895