The Role of Caspase-12 in Retinal Bystander Cell Death and Innate Immune Responses against MCMV Retinitis.

Abstract

(1) Background: caspase-12 is activated during cytomegalovirus retinitis, although its role is presently unclear. (2) Methods: caspase-12-/- (KO) or caspase-12+/+ (WT) mice were immunosup eyes were analyzed by plaque assay, TUNEL assay, immunohistochemical staining, western blotting, and real-time PCR. (3) Results: increased retinitis and a more extensive virus spread were detected in the retina of infected eyes of KO mice compared to WT mice at day 14 p.i. Compared to MCMV injected WT eyes, mRNA levels of interferons α, β and γ were significantly reduced in the neural retina of MCMV-infected KO eyes at day 14 p.i. Although similar numbers of MCMV infected cells, similar virus titers and similar numbers of TUNEL-staining cells were detected in injected eyes of both KO and WT mice at days 7 and 10 p.i., significantly lower amounts of cleaved caspase-3 and p53 protein were detected in infected eyes of KO mice at both time points. (4) Conclusions: caspase-12 contributes to caspase-3-dependent and independent retinal bystander cell death during MCMV retinitis and may also play an important role in innate immunity against virus infection of the retina.

• Authors: Xinyan Zhang, Jinxian Xu, Brendan Marshall, Zheng Dong, Sylvia B Smith, Ming Zhang
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 15 (Jul 29 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34360899 (Publication Type: Journal Article)

Chemical References

• Trp53 protein, mouse
• Tumor Suppressor Protein p53
• Interferons
• Casp12 protein, mouse
• Caspase 12

Topics

• Animals
• Apoptosis (genetics)
• Caspase 12 (deficiency, genetics)
• Cytomegalovirus Retinitis (enzymology, genetics, virology)
• Female
• Immunity, Innate (genetics)
• In Situ Nick-End Labeling (methods)
• Interferons (biosynthesis)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Muromegalovirus (physiology)
• Retina (enzymology, virology)
• Retinal Neurons (enzymology, virology)
• Signal Transduction (genetics)
• Tumor Suppressor Protein p53 (metabolism)
• Virus Replication (genetics)