title: Vaccination inhibits TLR2 transcription via suppression of GR nuclear translocation and binding to TLR2 promoter in porcine lung infected with Mycoplasma hyopneumoniae.
abstract: Toll-like receptors (TLRs) and glucocorticoid receptor (GR) act respectively as effectors of innate immune and stress responses. The crosstalk between them is critical for the maintenance of homeostasis during the immune response. Vaccination is known to boost adaptive immunity, yet it remains elusive whether vaccination may affect GR/TLR interactions following infection. Duroc×Meishan crossbred piglets were allocated to three groups. The control group (CC) received neither vaccination nor infection; the non-vaccinated infection group (NI) was artificially infected intratracheally with Mycoplasma hyopneumoniae (M. hyopneumoniae); while the vaccinated, infected group (VI) was vaccinated intramuscularly with inactivated M. hyopneumoniae one month before infection. The clinical signs and macroscopic lung lesions were significantly reduced by vaccination. However, vaccination did not affect the concentration of M. hyopneumoniae DNA in the lung. Serum cortisol was significantly decreased in both NI and VI pigs (P<0.01), but only VI pigs demonstrated significantly diminished nuclear GR content. TLRs 1-10 were all expressed in lung, among which TLR2 was the most abundant and was significantly up-regulated (P<0.05) in NI pigs, but not in VI pigs. Accordingly, GR binding to the GR response element on TLR2 promoter was significantly increased (P<0.05) in NI pigs, but not in VI pigs. These results suggest that the inhibition of GR nuclear translocation and binding to the TLR2 promoter, which results in diminished TLR2 expression, is associated with the protective effect of vaccination on M. hyopneumoniae-induced lung lesions in the pig.
authors.affiliation: Key Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, PR China. Electronic address: sunzhiyuan1984@163.com.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Sun
authors.forename: Maojun
authors.initials: M
authors.lastname: Liu
authors.forename: Huafeng
authors.initials: H
authors.lastname: Zou
authors.forename: Xian
authors.initials: X
authors.lastname: Li
authors.forename: Guoqing
authors.initials: G
authors.lastname: Shao
authors.forename: Ruqian
authors.initials: R
authors.lastname: Zhao
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000276:immunology; D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D004269:DNA, Bacterial / Q000032:analysis; D005786:Gene Expression Regulation / Q000276:immunology*; D006854:Hydrocortisone / Q000097:blood; D008168:Lung / Q000473:pathology; D045705:Mycoplasma hyopneumoniae / Q000276:immunology; D045729:Pneumonia of Swine, Mycoplasmal / Q000276:immunology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013552:Swine; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000378:metabolism*; D014611:Vaccination / Q000662:veterinary*; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D001428:Bacterial Vaccines; D004269:DNA, Bacterial; D011965:Receptors, Glucocorticoid; D051195:Toll-Like Receptor 2; D015164:Vaccines, Inactivated; D006854:Hydrocortisone
keywords: 11β-HSD; 11β-hydroxysteroid-dehydrogenases; Bnuclear factor κB, p38 MAPKp38 mitogen-activated protein kinase; CCU; ChIP; GC; GR; GRE; Glucocorticoid receptor; HPA; Mycoplasma hyopneumoniae; NF-κ; Pig; QPCR; TLR; TNF-; Toll-like receptor; Toll-like receptors; Transcriptional regulation; alphatumor necrosis factor alpha; chromatin immunoprecipitation; color changing unit; glucocorticoid; glucocorticoid receptor; glucocorticoid response element; hypothalamic–pituitary–adrenal, Mycoplasma hyopneumoniaeM. hyopneumoniae; real-time quantitative PCR