Cytosolic Double-Stranded DNA Induces Nonnecroptotic Programmed Cell Death in Trophoblasts via IFI16

The mechanisms underlying the immune defense by trophoblasts against pathogens remain ill defined. We demonstrated that placental cell death was increased upon in vivo exposure to Listeria monocytogenes. The death of infected cells is an important host innate defense mechanism. Meanwhile, double-str...

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Bibliographic Details
Published in:The Journal of infectious diseases 2014-11, Vol.210 (9), p.1476-1486
Main Authors: Chu, Xiao, Chen, Wei, Li, Ning, Hu, Xiao-Zhu, Du, Chong-Tao, Yu, Shui-Xing, Zhou, Min, Zhang, Xiao-Jing, Jiang, Gui-Mei, Han, Wen-Yu, Deng, Xu-Ming, Yang, Yong-Jun
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Bacteria
Caspases - metabolism
Cell death
Cell Death - drug effects
Cell Line
DNA - pharmacology
DNA, Bacterial - pharmacology
Female
Gene expression
Humans
Infections
Listeria monocytogenes - drug effects
Listeria monocytogenes - physiology
Listeriosis - microbiology
Male
Mice, Inbred C57BL
Necrosis
Nuclear Proteins - physiology
PATHOGENESIS AND HOST RESPONSE
Pathogens
Phosphoproteins - physiology
Pregnancy
Transfection
Trophoblasts
Trophoblasts - drug effects
Trophoblasts - microbiology
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Summary:The mechanisms underlying the immune defense by trophoblasts against pathogens remain ill defined. We demonstrated that placental cell death was increased upon in vivo exposure to Listeria monocytogenes. The death of infected cells is an important host innate defense mechanism. Meanwhile, double-stranded DNA (dsDNA) derived from intracellular bacteria or dsDNA viruses is emerging as a potent pathogen-associated molecular pattern recognized by host cells. We sought to characterize trophoblast death in response to cytosolic dsDNA challenge. Our results showed that dsDNA induced caspase-dependent and -independent cell death in human trophoblasts. However, necroptosis, a cell death pathway independent of caspase, could not be induced by dsDNA treatment, even in the presence of exogenously expressed RIPK3. L. monocytogenes-derived genomic DNA triggered a similar cell death pattern. Moreover, the cell death in response to dsDNA was IFI16 dependent. These data suggest that cytosolic dsDNA induces nonnecroptotic cell death in trophoblasts via IFI16, and this could contribute to placental barrier against infection.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiu272