Author
KIECKENS, E - Ghent University | |
RYBARCZYK - Ghent University | |
Li, Robert | |
VANROMPAY, D - Ghent University | |
COX, ERIC - Ghent University |
Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 12/5/2016 Publication Date: 12/21/2016 Citation: Kieckens, E., Rybarczyk, Li, R.W., Vanrompay, D., Cox, E. 2016. Potential immunosuppressive effects of E. coli O157:H7 experimental infection on the bovine host. Biomed Central (BMC) Genomics. 17:1049. https://doi.org/10.1186/s12864-016-3374-y. DOI: https://doi.org/10.1186/s12864-016-3374-y Interpretive Summary: Enterohaemorrhagic E. coli (EHEC) is among the most important foodborne pathogens. EHEC is transmitted to humans primarily through consumption of contaminated raw or undercooked meat products. While no clinical symptoms upon infection are observed, cattle are nevertheless a major carrier or natural reservoir of EHEC, such as E. coli O157:H7. In this study, we examined how the initial E. coli O157:H7 infection in cattle represses host immune respsones and regulates subsequent infection and heterogeneous shedding ability. Our findings provide novel insights into dyanmics of EHEC colonization in the gastrointestinal tract and should facilitate the development of strategies to identify and eliminate those so called "super-shedders", the cattle that shed E. coli O157:H7 at >104 colony-forming units (CFU) per gram of feces. Technical Abstract: Enterohaemorrhagic Escherichia coli (EHEC) bacteria, such as serotype O157:H7, are an important human pathogen responsible for global outbreaks of bloody diarrhea and hemolytic uremic syndrome. EHEC is frequently detected in cattle feces in slaughterhouses. As a result, cattle are the main natural reservoir of EHEC. However, cattle are asymptomatic carriers of the pathogen and do not show clinical symptoms upon infection. The ability of cattle shedding EHEC is regulated by host immune responses. We hypothesize that the suppression of certain pathways of the immune system by the initial EHEC infection makes cattle more prone to persistent colonization during subsequent infections. To test this theory, we conducted a transcriptome analysis using RNA-seq technology of the ileal Peyer’s patches and the recto-anal junction from calves that were infected either once, twice or that were never in contact with E. coli O157:H7. Our results show E. coli O157:H7 is able to repress various levels of innate and adaptive immune responses via a wide variety of mechanisms, including dramatically decreasing the expression of some key chemokines and cytokines, such as CCL20, IL-1, IL-8, and IL-12p40. Our findings should facilitate the development of effective measures to control EHEC colonization in ruminants,thereby reducing the spread to humans. |