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Series GSE171160 Query DataSets for GSE171160
Status Public on Apr 06, 2021
Title Subversion of host innate immunity by Rickettsia australis via a modified autophagic response in macrophages
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary We recently reported that the in vitro and in vivo survival of Rickettsia australis are Atg5-dependent, in association with an inhibited level of anti-rickettsial cytokine, IL-1β. In the present study, we sought to investigate how R. australis interacts with host innate immunity via an Atg5-dependent autophagic response. We found that the serum levels of IFN-γ and G-CSF in R. australis-infected Atg5flox/floxLyz-Cre mice were significantly less compared to Atg5flox/flox mice, accompanied by significantly lower rickettsial loads in tissues with inflammatory cellular infiltrations including neutrophils. R. australis infection differentially regulated a significant number of genes in bone marrow-derived macrophages (BMMs) in an Atg5-depdent fashion as determined by RNA sequencing and Ingenuity Pathway Analysis, including genes in the molecular networks of IL-1 family cytokines and PI3K-Akt-mTOR. The secretion levels of inflammatory cytokines, such as IL-1α, IL-18, TNF-α, and IL-6, by R. australis-infected Atg5flox/floxLyz-Cre BMMs were significantly greater compared to infected Atg5flox/flox BMMs. Interestingly, R. australis significantly increased the levels of phosphorylated mTOR and P70S6K at a time when the autophagic response is induced. Rapamycin treatment nearly abolished the phosphorylated mTOR and P70S6K but did not promote significant autophagic flux during R. australis infection. These results highlight that R. australis modulates an Atg5-dependent autophagic response, which is not sensitive to regulation by mTORC1 signaling in macrophages. Overall, we demonstrate that R. australis counteracts host innate immunity including IL-1β-dependent inflammatory response to support the bacterial survival via an mTORC1-resistant autophagic response in macrophages.
 
Overall design RNA-seq analysis (next-generation sequencing on R. australis-infected bone marrow-derived macrophages of Atg5 flox/flox mice and Atg5 flox/flox Lyz-Cre mice at 24 h p.i. .
 
Contributor(s) Bechelli JR, Rumfield CS, Widen S, Walker DH, Khanipov K, Fang R
Citation(s) 33912163
Submission date Mar 30, 2021
Last update date May 06, 2021
Contact name Rong Fang
E-mail(s) rofang@utmb.edu
Phone 4097470789
Organization name utmb
Department Pathology
Street address 301 University Blvd
City Galveston
State/province Texas
ZIP/Postal code 77555
Country USA
 
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (4)
GSM5220128 24hr_Cre_minus3_Un
GSM5220129 24hr_Cre_minus3_Ra-1
GSM5220130 24hr_Cre_plus1_Un-1
Relations
BioProject PRJNA718569
SRA SRP312748

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
GSE171160_RAW.tar 1.1 Mb (http)(custom) TAR (of TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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