biostudies-literatureNegretti NMInfectious Diseases and Microbial Immunology Post-doctoral Training Program at Washington State UniversityNIAID NIH HHSKonkel from the School of Molecular Biosciences, WSU Graduate School, and National Institutes of HealthNational Institutes of Health1-25https://www.ebi.ac.uk/biostudies/studies/S-EPMC7524355biostudies-literatureUnknown12(1)The symptoms of infectious diarrheal disease are mediated by a combination of a pathogen's virulence factors and the host immune system. <i>Campylobacter jejuni</i> 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 <i>C. jejuni</i>. 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 <i>C. jejuni</i> 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 <i>C. jejuni</i> wild-type strain, infection with the noninvasive <i>C. jejuni ∆ciaD</i> mutant resulted in a blunted inflammatory response, with less inflammatory cytokines and neutrophil markers. These findings indicate that intestinal inflammation is driven by <i>C. jejuni</i> virulence and that neutrophils are the predominant cell type responding to <i>C. jejuni</i> infection. We propose that this model can be used as a platform to study the early immune events during infection with intestinal pathogens.Gut microbesA porcine ligated loop model reveals new insight into the host immune response against <i>Campylobacter jejuni</i>.PMC7524355R01 AI083387R01AI125356GM094623T32 AI0070255T32AI007025R01 AI125356R01AI083387 and R21AI124144R21 AI124144Looft TBose SKonkel MENoh SNegretti NMYe YPokharel SMRagle CAMalavasi LMParker CTGourley CRHuynh SClair GAdkins JNKlima CLfalseA porcine ligated loop model reveals new insight into the host immune response against <i>Campylobacter jejuni</i>.The symptoms of infectious diarrheal disease are mediated by a combination of a pathogen's virulence factors and the host immune system. <i>Campylobacter jejuni</i> 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 <i>C. jejuni</i>. 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 <i>C. jejuni</i> 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 <i>C. jejuni</i> wild-type strain, infection with the noninvasive <i>C. jejuni ∆ciaD</i> mutant resulted in a blunted inflammatory response, with less inflammatory cytokines and neutrophil markers. These findings indicate that intestinal inflammation is driven by <i>C. jejuni</i> virulence and that neutrophils are the predominant cell type responding to <i>C. jejuni</i> infection. We propose that this model can be used as a platform to study the early immune events during infection with intestinal pathogens.2020-01-01T00:00:00Z2020 Nov2024-12-04T06:57:36.635Z2020-10-29T10:28:40ZS-EPMC75243553288753010.1080/19490976.2020.1814121