Abstract
Mycoplasma gallisepticum (MG) is the most economically significant mycoplasma pathogen of poultry that causes chronic respiratory disease (CRD) in chickens. Although miRNAs have been identified as a major regulator effect on inflammatory response, it is largely unclear how they regulate MG-induced inflammation. The aim of this study was to investigate the functional roles of gga-miR-451 and identify downstream targets regulated by gga-miR-451 in MG infection of chicken. We found that the expression of gga-miR-451 was significantly up-regulated during MG infection of chicken embryo fibroblast cells (DF-1) and chicken embryonic lungs. Overexpression of gga-miR-451 decreased the MG-induced inflammatory cytokine production, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), whereas inhibition of gga-miR-451 had the opposite effect. Gene expression data combined with luciferase reporter assays demonstrated that tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein zeta (YWHAZ) was identified as a direct target of gga-miR-451 in the context of MG infection. Furthermore, upregulation of gga-miR-451 significantly inhibited the MG-infected DF-1 cells proliferation, induced cell-cycle arrest, and promoted apoptosis. Collectively, our results demonstrate that gga-miR-451 negatively regulates the MG-induced production of inflammatory cytokines via targeting YWHAZ, inhibits the cell cycle progression and cell proliferation, and promotes cell apoptosis. This study provides a better understanding of the molecular mechanisms of MG infection.
Highlights
The host inflammatory response constitutes an essential immune defense against invasion by microbial pathogens
Mycoplasma gallisepticum (MG) Infection Significantly Upregulates gga-miR-451 Expression Microribonucleic acids (miRNA) sequencing was performed previously and a large variety of dysregulated miRNAs were identified in the lungs of MG-infected chicken embryos, and gga-miR-451 was down-regulated during MG infection [31]
We further investigated the expression of gga-miR-451 in MG-infected DF-1 cells at 48 h post-infection, and the result demonstrated that gga-miR-451 expression was up-regulated after MG infection (Figure 1B)
Summary
The host inflammatory response constitutes an essential immune defense against invasion by microbial pathogens. Mycoplasma gallisepticum (MG) is a common etiological cause of chronic respiratory disease (CRD) in chickens and infectious sinusitis in turkeys [2], which feature inflammation in respiratory tract (trachea, lungs, and air sacs) [3,4]. MG can invade, survive, and multiply inside chicken embryonic fibroblasts (CEF) and HeLa cells in vitro [7,8,9]. MG interacts with host respiratory epithelial cells and generates an inflammatory response, resulting in increased levels of cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-2 (IL-2) [10]. The increased levels of inflammatory mediators appear to play a protective role or to initiate an irreversible immune response leading to cell death [11]. MG-HS strain is a virulence strain isolated from a chicken farm in Hubei Province of China, which is used for further experiments [12,13]
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