Altered microRNA expression and pre-mRNA splicing events reveal new mechanisms associated with early stage Mycobacterium avium subspecies paratuberculosis infection.
The molecular regulatory mechanisms of host responses to Mycobacterium avium subsp. paratuberculosis (MAP) infection during the early subclinical stage are still not clear. In this study, surgically isolated ileal segments in newborn calves (n = 5) were used to establish in vivo MAP infection adjacent to an uninfected control intestinal compartment. RNA-Seq was used to profile the whole transcriptome (mRNAs) and the microRNAome (miRNAs) of ileal tissues collected at one-month post-infection. The most related function of the differentially expressed mRNAs between infected and uninfected tissues was "proliferation of endothelial cells", indicating that MAP infection may lead to the over-proliferation of endothelial cells. In addition, 46.2% of detected mRNAs displayed alternative splicing events. The pre-mRNA of two genes related to macrophage maturation (monocyte to macrophage differentiation-associated) and lysosome function (adenosine deaminase) showed differential alternative splicing events, suggesting that specific changes in the pre-mRNA splicing sites may be a mechanism by which MAP escapes host immune responses. Moreover, 9 miRNAs were differentially expressed after MAP infection. The integrated analysis of microRNAome and transcriptome revealed that these miRNAs might regulate host responses to MAP infection, such as "proliferation of endothelial cells" (bta-miR-196 b), "bacteria recognition" (bta-miR-146 b), and "regulation of the inflammatory response" (bta-miR-146 b).
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
Guanxiang
G
Liang
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
Nilusha
N
Malmuthuge
UWA Institute of Agriculture and School of Animal Biology, University of Western Australia, Crawley, WA, Australia.|Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Yongjuan
Y
Guan
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.|Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agriculture University, Wuhan, Hubei, China.
Yuwei
Y
Ren
Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, Canada.|School of Public Health, University of Saskatchewan, Saskatoon, SK, Canada.
Philip J
PJ
Griebel
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
Le Luo
le L
Guan
D000818:Animals; D002417:Cattle; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000473:pathology; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D007082:Ileum / Q000473:pathology*; D057131:Immune Evasion; D035683:MicroRNAs / Q000032:analysis*; D016927:Mycobacterium avium subsp. paratuberculosis / Q000254:growth & development*; D010283:Paratuberculosis / Q000473:pathology*; D012322:RNA Precursors / Q000378:metabolism*; D012326:RNA Splicing
D035683:MicroRNAs; D012322:RNA Precursors