Cellular prion protein participates in the regulation of inflammatory response and apoptosis in BV2 microglia during infection with Mycobacterium bovis.
The cellular prion protein (PrP(C)) is a glycoprotein anchored by glycosylphosphatidylinositol to the cell surface and is abundantly expressed in the central nervous system. A previous study has shown that PrP(C) contributes to the establishment of infections with intracellular bacteria in macrophages. In the present work, we investigated the role of PrP(C) in the response of BV2 microglia to Mycobacterium bovis infection. For this purpose, we examined the mRNA expression of prion protein gene (PRNP) upon M. bovis infection and analyzed the effect of siRNA-mediated disruption of PRNP on different parameters of microglial activation and apoptosis in M. bovis-infected microglia. We found that M. bovis infection induced a gradual increase in PRNP mRNA level and that siRNA-mediated silencing of PRNP in M. bovis-infected microglia reduced M. bovis-induced upregulation of pro-inflammatory factors, increased the rate of apoptosis in infected microglia, promoted the intrinsic apoptotic pathway, and downregulated the extrinsic apoptotic pathway. We conclude that PrP(C) participates in the regulation of the response of microglia to M. bovis infection through the upregulation of pro-inflammatory cytokines and the modulation of apoptosis by interference with the intrinsic apoptotic pathway.
State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China. dingtianjian_1986@126.com
Tianjian
T
Ding
Xiangmei
X
Zhou
Mohammed
M
Kouadir
Fushan
F
Shi
Yang
Y
Yang
Jin
J
Liu
Min
M
Wang
Xiaomin
X
Yin
Lifeng
L
Yang
Deming
D
Zhao
D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D017628:Microglia / Q000378:metabolism* / Q000382:microbiology; D009163:Mycobacterium bovis; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D012333:RNA, Messenger