A porcine ligated loop model reveals new insight into the host immune response against Campylobacter jejuni
| Autor: | Nicholas M Negretti, Yinyin Ye, Lais M Malavasi, Swechha M Pokharel, Steven Huynh, Susan Noh, Cassidy L Klima, Christopher R Gourley, Claude A Ragle, Santanu Bose, Torey Looft, Craig T Parker, Geremy Clair, Joshua N Adkins, Michael E Konkel |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Gut Microbes, Vol 12, Iss 1 (2020) |
| Druh dokumentu: | article |
| ISSN: | 1949-0976 1949-0984 19490976 |
| DOI: | 10.1080/19490976.2020.1814121 |
| 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: | Directory of Open Access Journals |
| Externí odkaz: |
|