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Series GSE147629 Query DataSets for GSE147629
Status Public on Oct 07, 2020
Title Development of an in vivo ligated loop model reveals new insight into the host immune response against Campylobacter jejuni
Organism Campylobacter jejuni
Experiment type Expression profiling by high throughput sequencing
Summary The symptoms of infectious diarrheal disease are mediated by the interplay between the host and pathogen. Campylobacter jejuni is the leading bacterial cause of diarrhea worldwide due to its near-ubiquitous zoonotic association with poultry. One of the outstanding questions is what factors drive the intestinal inflammation during the development of C. jejuni-mediated disease. Specifically, it is not known the extent to which the bacteria are responsible for the diarrheal symptoms via cell necrosis, or whether there is immune cell recruitment prior to tissue damage. To determine the stepwise process of inflammation that leads to diarrhea, we used a piglet ligated intestinal loop model to study the intestinal environment in response to C. jejuni. Pigs were chosen due to the anatomical similarity of the porcine intestine to the human intestine, as the basis of disease modeling is to understand the process of human disease. Using immunoassays and proteomic approaches, we found that neutrophils are most likely the predominant cell type recruited to the intestines of C. jejuni infected animals. In the lumen of the intestine, a number of neutrophil related proteins increased during C. jejuni infection, including proteins related to neutrophil migration (elastase and MMP9), actin reorganization and bacterial uptake (Cdc42, WAVE-2, and Arp2/3), and antimicrobial proteins (lipocalin-2, myeloperoxidase, S100A8, and S100A9). The appearance of neutrophils also corresponds with increases of both IL-8 and TNF-a. Compared to infection with the C. jejuni wild-type strain, infection with the noninvasive C. jejuni ∆ciaD mutant resulted in a blunted inflammatory response, with less inflammatory cytokines and neutrophil markers. These findings indicate that intestinal inflammation is driven by C. jejuni virulence, and that resident intestinal cells precipitate the inflammatory response. Using this new disease model, we have developed a platform to study the early immune events during C. jejuni infection.
 
Overall design Minnesota mini pigs were used in a ligated intestinal loop model of infection, where the pigs were maintained under general anesthesia and 1 x 10^10 C. jejuni was inoculated into ~10 cm discreet ligated intestinal segments. The pigs were maintained for 3, 6, 12, or 30 hours, and luminal C. jejuni was recovered and sequenced. Three animals each were included in the analysis, with two technical replicates (loops) within each animal. These results were compared to co-culture with cultured IPEC-J2 cells for 2.5 or 4 hours (two samples at each time point). All samples were compared to the respective 'input' sample, which is C. jejuni grown in MH broth for 18 hours.
 
Contributor(s) Negretti NM, Ye Y, Malavasi LM, Pokharel SM, Huynh S, Noh S, Gourley CR, Ragle CA, Bose S, Looft T, Parker CT, Clair G, Adkins JN, Konkel ME
Citation(s) 32887530
Submission date Mar 27, 2020
Last update date Oct 07, 2020
Contact name Michael E Konkel
E-mail(s) konkel@wsu.edu
Organization name Washington State University
Street address PO Box 647520
City Pullman
State/province WA
ZIP/Postal code 99164
Country USA
 
Platforms (1)
GPL22824 Illumina MiSeq (Campylobacter jejuni)
Samples (78)
GSM4436515 Pig WT 3 hour Animal #1 Loop #1
GSM4436516 Pig WT 3 hour Animal #1 Loop #3
GSM4436517 Pig WT 3 hour Animal #2 Loop #1
Relations
BioProject PRJNA615847
SRA SRP254305

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

Supplementary file Size Download File type/resource
GSE147629_IPEC_gene_counts.csv.gz 36.0 Kb (ftp)(http) CSV
GSE147629_Pig_gene_counts.csv.gz 109.3 Kb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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