JOURNAL ARTICLE

Intrinsic apoptosis and cytokine induction regulated in human tonsillar epithelial cells infected with enterovirus A71

Menghuai Sun, Kunlong Yan, Chunyang Wang, Jiao Xing, Zhaojun Duan, Yu Jin, Carol J Cardona, Zheng Xing
PloS One 2021, 16 (1): e0245529
33481814
Enterovirus A71 (EV-A71) has emerged as a clinically important neurotropic virus following poliovirus eradication. Recent studies have shown that human tonsillar epithelial cell lines (UT-SCC-60A and UT-SCC-60B) were susceptible to EV-A71, suggesting that human tonsillar crypt epithelium could be important in EV-A71 pathogenesis. However, the mechanism about how EV-A71 infects the upper oro-digestive tract remains largely unclear. In this study, we demonstrated that the human tonsillar epithelial cells infected with EV-A71 underwent apoptotic, in which cytochrome c was released from the mitochondria to the cytosol and caspase-9 was activated, while caspase-2 and -8 were not cleaved or activated during the infection. A selective inhibitor of caspase-9, Z-LEHD-FMK, inhibited the cleavage of the executioner caspase-3 and -7, indicating that only mitochondria-mediated intrinsic apoptotic pathway was activated in EV-A71-infected tonsillar epithelial cells. No evidence of pyroptosis or necroptosis was involved in the cell death. EV-A71 infection induced interferon, pro-inflammatory cytokines and chemokines, including IFN-β, IL-6, CCL5, and TNF-α in tonsillar epithelial cells, which may play a critical role in EV-A71-caused herpangina. Our data indicated that the induction of the cytokines was partially regulated by the mitogen-activated protein kinases (MAPKs) signaling pathway. The findings unveiled the host response to EV-A71 and its regulation mechanism, and will further our understanding the significance about the tonsillar crypt epithelium as the initial and primary portal in viral pathogenesis for EV-A71 infection.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read
33481814
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"