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Title: Mus musculus : Mus musculus Transcriptome or Gene expression      
keywords:
transcriptome
ID:
PRJNA311622
description:
Alveolar macrophage (AM) dysfunction contributes to susceptibility to secondary bacterial pneumonia after influenza, a major cause of morbidity and mortality. We investigated whether immunomodulation of the AM scavenger receptor macrophage receptor with collagenous structure (MARCO) could improve host defense and resistance to secondary pneumococcal pneumonia. In vitro, interferon- (IFN) down-regulated MARCO expression by AM-like human monocyte-derived macrophages (HMDMs), but the Nrf2 activator, sulforaphane (SFN), restored MARCO expression and improved bacterial phagocytosis. In a murine model of post-influenza pneumonia, sulforaphane improved survival in wild-type but not in MARCO-deficient mice. Initially, elevated IFN levels following influenza infection coincided with attenuated MARCO expression in the lungs. However, as IFN levels returned to normal levels on post-influenza day 11, there was a striking increase of MARCO expression compared to the low level observed on day 9. RNA sequencing analysis of lung macrophages purified from these days identified increased expression of Akt coinciding with increases in MARCO. The Akt activator SC79 significantly increased MARCO expression on IFN-treated AM-like HMDMs, and improved mouse survival in post-influenza pneumococcal pneumonia. Transcription factor analysis indicated a role for transcription factor E-box (TFEB) in MARCO recovery. Overexpression of TFEB in THP-1 cells led to marked increases in MARCO mRNA levels. SC79-induced MARCO expression in IFN-treated HMDMs was abrogated in TFEB-knockdown cells compared to controls. The results suggest that Akt regulates MARCO expression through effects on the transcription factor TFEB in the setting of post-influenza bacterial pneumonia. The data identify novel regulators of AM MARCO expression after influenza, and broaden the range of potential immunomodulatory targets to improve host resistance to post-influenza secondary pneumonia.
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA311622
authentication:
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authorization:
none
name:
Mus musculus
ncbiID:
ncbitax:10090
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject