A porcine ligated loop model reveals new insight into the host immune response against Campylobacter jejuni

Autor: Swechha M. Pokharel, Claude A. Ragle, Geremy Clair, Christopher R. Gourley, Yinyin Ye, Nicholas M. Negretti, Joshua N. Adkins, Santanu Bose, Lais M Malavasi, Cassidy L. Klima, Steven Huynh, Michael E. Konkel, Torey Looft, Susan Noh, Craig T. Parker
Rok vydání: 2020
Předmět:
0301 basic medicine
Proteome
Neutrophils
Swine
0302 clinical medicine
Campylobacter Infections
Intestine
Small
Intestinal Mucosa
innate immunity
Virulence
biology
pathogenesis
Gastroenterology
Infectious Diseases
Neutrophil elastase
Myeloperoxidase
Cytokines
Swine
Miniature
030211 gastroenterology & hepatology
medicine.symptom
intestinal disease
Research Article
Research Paper
Microbiology (medical)
Virulence Factors
Inflammation
Microbiology
Campylobacter jejuni
Cell Line
Proinflammatory cytokine
03 medical and health sciences
proteomics
Immune system
medicine
Animals
lcsh:RC799-869
Innate immune system
Disease model
Macrophages
Epithelial Cells
biology.organism_classification
Gastrointestinal Microbiome
Disease Models
Animal
030104 developmental biology
biology.protein
lcsh:Diseases of the digestive system. Gastroenterology
Transcriptome
Zdroj: Gut Microbes
article-version (VoR) Version of Record
Gut Microbes, Vol 12, Iss 1 (2020)
ISSN: 1949-0984
1949-0976
Popis: The symptoms of infectious diarrheal disease are mediated by a combination of a pathogen’s virulence factors and the host immune system. 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 to what extent the bacteria are responsible for the diarrheal symptoms via intestinal cell necrosis versus immune cell initiated 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 response to C. jejuni. Pigs were chosen due to the anatomical similarity between the porcine and the human intestine. We found that the abundance of neutrophil related proteins increased in the intestinal lumen during C. jejuni infection, including proteins related to neutrophil migration (neutrophil elastase and MMP9), actin reorganization (Arp2/3), and antimicrobial proteins (lipocalin-2, myeloperoxidase, S100A8, and S100A9). The appearance of neutrophil proteins also corresponded with increases of the inflammatory cytokines IL-8 and TNF-α. 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 neutrophils are the predominant cell type responding to C. jejuni infection. We propose that this model can be used as a platform to study the early immune events during infection with intestinal pathogens.
Databáze: OpenAIRE
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