GSE32619 Host resistance to pulmonary infection with Mycobacterium tuberculosis is mediated by IL-1alpha.

Contributors : Richard P Beyer ; Nelson C DiPaolo ; Shahin Shafiani ; Tracey Day ; Thalia Papayannoupoulou ; Yoichiro Iwakura ; Richard A Flavell ; Theodor K Bamler ; David W Russell ; Sarah J Dunstan ; Thomas R Hawn ; Amber Burt ; Brian Browning ; Gail P Jarvik ; David Sherman ; Kevin Urdah ; Dmitry M ShayakhmetovSeries Type : Expression profiling by arrayOrganism : Mus musculusBackground: M.tuberculosis is one of the most prevalent and deadly human pathogens. The molecular mechanisms determining the outcomes of an infection with M.tuberculosis, that range from resistance to an active progressive disease, remain incompletely understood. Here we provide the evidence that IL-1alpha plays a critical and non-redundant role in enabling host resistance to pulmonary M.tuberculosis infection in mice that develop functional pathogen-specific adaptive immunity. Mechanistically, IL-1alpha-deficient mice fail to control M.tuberculosis replication in vivo at a level of individual infected cells and succumb to progressive disease at the late phase of infection. Furthermore, we show that IL-1alpha from hematopoietic compartment through IL-1RI operates upstream of TNFRI-signaling pathway and the lack of IL-1alpha leads to the continuous influx of monocytes that acquire a hyper-inflammatory phenotype and contribute to pathology, rather than to a pathogen control. Cell-type-specific restoration of IL-1alpha expression in CD11c+ subsets of lung leukocytes resulted in reduced levels of ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Mus musculus Source Type: research