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E-GEOD-44848 - Type I IFN signaling promotes local inflammation in pulmonary tuberculosis

Status
Released on 31 December 2013, last updated on 2 June 2014
Organism
Mus musculus
Samples (24)
Array (1)
Protocols (7)
Description
The critical role of type I IFN (IFN I ) in viral disease is thoroughly documented while their function in bacterial infection remains ambiguous. General interest in biological functions of IFN I in Mycobacterium tuberculosis (Mtb) infection was raised by the identification of a distinct IFN I gene expression signature in tuberculosis (TB) patients. Here we demonstrate that TB-susceptible mice lacking the receptor for IFN I (IFNAR1) were protected from death upon aerogenic infection with Mtb. Increased survival was accompanied by reduced bacterial burden and ameliorated lung pathology as well as diminished production of proinflammatory IL-1?, among other cytokines. IFNAR1 signaling did not affect T cell responses, but markedly altered migration of inflammatory monocytes and neutrophils to the lung during pulmonary TB. This process was orchestrated by presence of IFNAR1 in both immune and tissue-resident radioresistant cells. IFNAR1-driven TB susceptibility was initiated by CXCL5/CXCL1-driven accumulation of neutrophils into alveoli and subsequently a distinct compartmentalization of Mtb in lung phagocytes. We conclude that IFN I alters early innate events at the site of Mtb invasion leading to unleashed inflammation. Hence, our data furnish a mechanistic explanation for the detrimental role of IFN I in pulmonary TB. dual-color color-swap
Experiment type
transcription profiling by array 
Contacts
Hans-Joachim Mollenkopf <mollenkopf@mpiib-berlin.mpg.de>, Anca Dorhoi, January Weiner, Stefan H Kaufmann, Vladimir Yeremeev
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-44848.idf.txt
Sample and data relationshipE-GEOD-44848.sdrf.txt
Raw data (1)E-GEOD-44848.raw.1.zip
Processed data (1)E-GEOD-44848.processed.1.zip
Array designA-MEXP-724.adf.txt
Links