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Series GSE198771 Query DataSets for GSE198771
Status Public on Apr 03, 2022
Title Analysis of resident peritoneal macrophage's transcriptome in WT and CGD mice
Organism Mus musculus
Experiment type Expression profiling by array
Summary The leukocyte NADPH oxidase 2 (NOX2) plays a key role in pathogen killing and immunoregulation. Genetic defects in NOX2 result in chronic granulomatous disease (CGD), associated with microbial infections and inflammatory disorders, often involving the lung. Alveolar macrophages (AM) are the predominant immune cell in the airways at steady state, and limiting their activation is important given constant exposure to inhaled materials, yet the importance of NOX2 in this process is not well-understood. Here, we show a previously undescribed role for NOX2 in maintaining lung homeostasis by suppressing AM activation, as studied using CGD mice or mice with selective loss of NOX2 primarily in macrophages. AM lacking NOX2 have increased cytokine responses to TLR2 and TLR4 stimulation ex vivo. Moreover, between 4 and 12 weeks of age, mice with global NOX2 deletion developed an activated CD11bhigh subset of AM with epigenetic and transcriptional profiles reflecting immune activation compared to WT AM. The presence of CD11bhigh AM in CGD mice correlated with increased numbers of alveolar neutrophils and proinflammatory cytokines at steady state as well as increased lung inflammation following insults. Moreover, deletion of NOX2 primarily in macrophages was sufficient for mice to develop an activated CD11bhigh AM subset and accompanying pro-inflammatory sequela. Additionally, we showed that the altered resident macrophage transcriptional profile in the absence of NOX2 is tissue-specific as these changes were not seen in resident peritoneal macrophages. Thus, these data demonstrate that absence of NOX2 in alveolar macrophages leads to their pro-inflammatory remodeling and dysregulates alveolar homeostasis.
Overall design Resident Peritoneal macrophages from WT and CGD mice were sorted into RPMI 1640 with 20% of FBS
Contributor(s) Sourav B, Wei Y, Juhi B, Mary C D
Citation(s) 35357446
Submission date Mar 16, 2022
Last update date Apr 05, 2022
Contact name Mary C Dinauer
Organization name Washington University In St Louis
Department Pathology & Immunology
Street address 660 South Euclid Ave
City St Louis
State/province Missouri
ZIP/Postal code 63110
Country USA
Platforms (1)
GPL11202 Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version)
Samples (12)
GSM5956745 WRPM F4/80high 1
GSM5956746 WRPM F4/80high 2
GSM5956747 WRPM F4/80high 3
This SubSeries is part of SuperSeries:
GSE198778 The leukocyte NADPH oxidase 2 (NOX2) plays a key role in pathogen killing and immunoregulation
BioProject PRJNA816859

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE198771_RAW.tar 109.7 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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