title: Distinct peripheral blood RNA responses to Salmonella in pigs differing in Salmonella shedding levels: intersection of IFNG, TLR and miRNA pathways.
abstract: Transcriptomic analysis of the response to bacterial pathogens has been reported for several species, yet few studies have investigated the transcriptional differences in whole blood in subjects that differ in their disease response phenotypes. Salmonella species infect many vertebrate species, and pigs colonized with Salmonella enterica serovar Typhimurium (ST) are usually asymptomatic, making detection of these Salmonella-carrier pigs difficult. The variable fecal shedding of Salmonella is an important cause of foodborne illness and zoonotic disease. To investigate gene pathways and biomarkers associated with the variance in Salmonella shedding following experimental inoculation, we initiated the first analysis of the whole blood transcriptional response induced by Salmonella. A population of pigs (n = 40) was inoculated with ST and peripheral blood and fecal Salmonella counts were collected between 2 and 20 days post-inoculation (dpi). Two groups of pigs with either low shedding (LS) or persistent shedding (PS) phenotypes were identified. Global transcriptional changes in response to ST inoculation were identified by Affymetrix Genechip® analysis of peripheral blood RNA at day 0 and 2 dpi. ST inoculation triggered substantial gene expression changes in the pigs and there was differential expression of many genes between LS and PS pigs. Analysis of the differential profiles of gene expression within and between PS and LS phenotypic classes identified distinct regulatory pathways mediated by IFN-γ, TNF, NF-κB, or one of several miRNAs. We confirmed the activation of two regulatory factors, SPI1 and CEBPB, and demonstrated that expression of miR-155 was decreased specifically in the PS animals. These data provide insight into specific pathways associated with extremes in Salmonella fecal shedding that can be targeted for further exploration on why some animals develop a carrier state. This knowledge can also be used to develop rational manipulations of genetics, pharmaceuticals, nutrition or husbandry methods to decrease Salmonella colonization, shedding and spread.
authors.affiliation: Department of Animal Science, Iowa State University, Ames, Iowa, United States of America.
authors.forename: Ting-Hua
authors.initials: TH
authors.lastname: Huang
authors.forename: Jolita J
authors.initials: JJ
authors.lastname: Uthe
authors.forename: Shawn M D
authors.initials: SM
authors.lastname: Bearson
authors.forename: Cumhur Yusuf
authors.initials: CY
authors.lastname: Demirkale
authors.forename: Dan
authors.initials: D
authors.lastname: Nettleton
authors.forename: Susan
authors.initials: S
authors.lastname: Knetter
authors.forename: Curtis
authors.initials: C
authors.lastname: Christian
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Ramer-Tait
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wannemuehler
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Tuggle
mesh_terms: D000818:Animals; D019540:Area Under Curve; D057138:Bacterial Shedding / Q000502:physiology*; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D058977:Molecular Sequence Annotation; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D012481:Salmonella Infections, Animal / Q000097:blood* / Q000235:genetics / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics*; D034421:Sus scrofa / Q000097:blood / Q000145:classification / Q000235:genetics / Q000382:microbiology*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D007371:Interferon-gamma