Avian resistance to Campylobacter jejuni colonization is associated with an intestinal immunogene expression signature identified by mRNA sequencing.
Item Type:Journal Article
Citation:Connell S, Meade KG, Allan B, Lloyd AT, Kenny E, Cormican P, Morris DW, Bradley DG, O'Farrelly C, Avian resistance to Campylobacter jejuni colonization is associated with an intestinal immunogene expression signature identified by mRNA sequencing., PloS one, 7, 8, 2012, e40409
journal.pone.0040409.pdf (Published (publisher's copy) - Peer Reviewed) 708.7Kb
Campylobacter jejuni is the most common cause of human bacterial gastroenteritis and is associated with several post-infectious manifestations, including onset of the autoimmune neuropathy Guillain-Barre syndrome, causing significant morbidity and mortality. Poorly-cooked chicken meat is the most frequent source of infection as C. jejuni colonizes the avian intestine in a commensal relationship. However, not all chickens are equally colonized and resistance seems to be genetically determined. We hypothesize that differences in immune response may contribute to variation in colonization levels between susceptible and resistant birds. Using high-throughput sequencing in an avian infection model, we investigate gene expression associated with resistance or susceptibility to colonization of the gastrointestinal tract with C. jejuni and find that gut related immune mechanisms are critical for regulating colonization. Amongst a single population of 300 4-week old chickens, there was clear segregation in levels of C. jejuni colonization 48 hours post-exposure. RNAseq analysis of caecal tissue from 14 C. jejuni-susceptible and 14 C. jejuni-resistant birds generated over 363 million short mRNA sequences which were investigated to identify 219 differentially expressed genes. Significantly higher expression of genes involved in the innate immune response, cytokine signaling, B cell and T cell activation and immunoglobulin production, as well as the renin-angiotensin system was observed in resistant birds, suggesting an early active immune response to C. jejuni. Lower expression of these genes in colonized birds suggests suppression or inhibition of a clearing immune response thus facilitating commensal colonization and generating vectors for zoonotic transmission. This study describes biological processes regulating C. jejuni colonization of the avian intestine and gives insight into the differential immune mechanisms incited in response to commensal bacteria in general within vertebrate populations. The results reported here illustrate how an exaggerated immune response may be elicited in a subset of the population, which alters host-microbe interactions and inhibits the commensal state, therefore having wider relevance with regard to inflammatory and autoimmune disease.
Type of material:Journal Article
Series/Report no:PloS one;
Availability:Full text available
Keywords:alpha4 integrin; antigen; CD79b antigen; cell adhesion molecule; CXCL13 chemokine; CXCL2 chemokine; immunoglobulin lambda chain; interferon regulatory factor 4; interleukin 8; lectin; lysozyme; messenger RNA; pleckstrin; reduced nicotinamide adenine dinucleotide phosphate; reduced nicotinamide adenine dinucleotide phosphate oxidase; toll like receptor 1; transcription factor PAX5; tumor necrosis factor receptor associated factor 3; tumor necrosis factor receptor associated factor 5
Showing items related by title, author, creator and subject.
Poxviral protein A52 stimulates p38 mitogen-activated protein kinase (MAPK) activation by causing tumor necrosis factor receptor-associated factor 6 (TRAF6) self-association leading to transforming growth factor ß-activated kinase 1 (TAK1) recruitment. BOWIE, ANDREW (2013)Vaccinia virus encodes a number of proteins that inhibit and manipulate innate immune signaling pathways that also have a role in virulence. These include A52, a protein shown to inhibit IL-1- and Toll-like receptor-stimulated ...
Clumping factor A interaction with complement factor I increases C3b cleavage on the bacterial surface of Staphylococcus aureus, and decreases complement-mediated phagocytosis FOSTER, TIMOTHY; GEOGHEGAN, JOAN (2010)The human complement system is important in the immunological control of Staphylococcus aureus infection. We showed previously that S. aureus surface protein clumping factor A (ClfA), when expressed in recombinant form, ...