|Bao, Hua - University Of Alberta|
|Kommadath, Arun - University Of Alberta|
|Liang, Guanxiang - University Of Alberta|
|Sun, Xu - University Of Alberta|
|Arantes, Adriano - University Of Alberta|
|Tuggle, Christopher - Iowa State University|
|Plastow, Graham - University Of Alberta|
|Stothard, Paul - University Of Alberta|
|Guan, Le Luo - University Of Alberta|
Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/6/2015
Publication Date: 7/31/2015
Citation: Bao, H., Kommadath, A., Liang, G., Sun, X., Arantes, A.S., Tuggle, C.K., Plastow, G.S., Bearson, S.M., Stothard, P., Guan, L. 2015. Genome-wide whole blood microRNAome and transcriptome analyses reveal miRNA-mRNA regulated host response to foodborne pathogen Salmonella infection in swine. Scientific Reports. 5:12620. doi: 10.1038/srep12620.
Interpretive Summary: Salmonella enterica serovar Typhimurium is a Gram-negative enteric pathogen which causes morbidity, mortality and economic loss worldwide. Salmonella causes a wide range of infections, including gastroenteritis, typhoid fever, bacteremia and endovascular infections. Pigs are an important source of salmonellosis in humans, and salmonellosis in pigs contributes to significant economic losses to the pig industry. To reduce the incidence and severity of Salmonella infections, a better understanding of the regulatory mechanisms of the host's immune response to Salmonella is needed to identify potenial targets for disease prevention. In this study, the response of pigs to Salmonella was evaluated by monitoring the expression of their genes. We show a signficant change in a distinct group of gene expression regulators, called microRNA. Specifically, we identified microRNAs that regulate critical immune response genes. For example, challenging the pigs with Salmonella caused the expression of microRNA miR-214 to decrease, while the immune genes that are negatively regulated by miR-214 were increased. Further investigation of these new candidates of porcine immune regulation during Salmonella infection will determine if modulation of their expression could improve the pig's response to Salmonella exposure, thereby improving animal health and food safety.
Technical Abstract: MicroRNAs (miRNAs) are important regulators of gene expression and play key roles in several biological processes. However, little is known about the role of miRNAs in regulating genes involved in host response to bacterial infection. Here, we present a systematic study of miRNA and mRNA profiles from whole blood of pigs upon Salmonella challenge. A total of 62 miRNAs were differentially expressed (DE) post infection (FDR less than 0.1). An integrative analysis of DE miRNAs and mRNAs using sequence-based miRNA target prediction and negative correlation of miRNA-mRNA profiles identified miR-214 and miR-331-3p as potential new candidates associated with Salmonella infection. This bioinformatics analysis suggested that these miRNAs regulate several critical immune-related genes including natural resistance-associated macrophage protein 1 (NRAMP1), leukocyte immunoglobulin-like receptor-like (LILR-like) and Vav2 guanine nucleotide exchange factor (VAV2). We showed that challenged pigs had reduced miR-214 expression and increased miR-331-3p expression in whole blood. Conversely, the expression of the proposed targets of miR-214 (NRAMP1 and LILR-like) increased following challenge, while the expression of the proposed target of miR-331-3p (VAV2) decreased. The regulatory control by these miRNAs of their predicted target genes was confirmed by in vitro assays. Salmonella infection in pigs causes significant changes in miRNA expression. Our results also suggest the important roles of miRNAs in regulating NRAMP1, LILR-like and VAV2 in response to bacterial infection.