Mycobacterium tuberculosis H37Rv infection regulates alternative splicing in Macrophages.
OBJECTIVE
The objective of this study was to evaluate the expression of genes encoding SR proteinsand alternative splicing of IL4 and TLR4 in Mycobacterium tuberculosis (M. tb) H37Rv-infected macrophages.


MATERIALS AND METHODS
THP-1 cells were induced to differentiate into macrophages with 200 nM PMA, and H37Rv strains were used for macrophage infection. After RNA extraction, qRT-PCR was performed to evaluate the expression of many SR proteins as well as the alternative splicing of IL4 and TLR4.


RESULTS
IL4 and TLR4 play significant roles in host immunity to tuberculosis. The level of IL-4 splice variants in THP-1 cells increased after M. tb H37Rv infection. Three splice variants of TLR4 were detected in M. tb-infected THP-1 cells, when compared with uninfected controls; the expression level of these splicing variants in M. tb-infected THP-1 cell was down-regulated. Since SR proteins are RNA-binding proteins that regulate RNA splicing, the expression of SR proteins was examined, and SRSF2 and SRSF3 were significantly down-regulated. In addition, splicing factors SRp75 and SF3a were also significantly down-regulated post M. tb infection.


CONCLUSION
Our findings indicate that alternative splicing may be involved in host gene regulation post M. tb infection of macrophage cells.
['Zhang|Wei|W|', 'Niu|Chen|C|', 'Fu|Rui-Yang|RY|', 'Peng|Zheng-Yu|ZY|']
D002454:Cell Differentiation D054884:Host-Pathogen Interactions D006801:Humans D015847:Interleukin-4 D008264:Macrophages D009169:Mycobacterium tuberculosis D012326:RNA Splicing D000072260:RNA Splicing Factors D000068103:Serine-Arginine Splicing Factors D015398:Signal Transduction D000074084:THP-1 Cells D013755:Tetradecanoylphorbol Acetate D051197:Toll-Like Receptor 4
Mycobacterium tuberculosis alternative splicing IL4 TLR4 SR proteins