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Richard D Dix, Christine Iris Alston, Hsin Chien; Pyroptosis and AIDS-related human cytomegalovirus (HCMV) retinitis: Caspase-1-dependent or caspase-1-independent interleukin-1β expression in response to HCMV infection is cell-type dependent. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2818.
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Pyroptosis, a cell death pathway different from apoptosis and necroptosis, is triggered by active caspase-1. Secretion of interleukin-1β (IL-1β) and IL-18 coincides with pyroptosis-associated cell death. We showed previously that caspase-1, IL-1β, and IL-18 mRNAs are upregulated within murine cytomegalovirus (MCMV)-infected eyes of mice with retrovirus-induced immunosuppression (MAIDS), a finding that suggests a role for pyroptosis in AIDS-related HCMV retinitis pathogenesis. This observation prompted us to investigate the expression of these pyroptosis-related molecules in various cell types during productive (lytic) HCMV infection.
Cultures of freshly isolated human peripheral blood mononuclear cells (PBMCs) as well as monolayers of human retinal pigment epithelial cells (ARPE-19 cells), immortalized human T-lymphocytes (Jurkat cells), and human lung fibroblasts (MRC-5 cells) were inoculated with HCMV (Towne) (moi = 5) or maintenance medium (control), harvested at 10 min to 48 hr postinfection (pi), and compared by quantitative real time RT-PCR assay for caspase-1, IL-1β, and IL-18 mRNA levels.
When compared with mock-infected cells, HCMV-infected ARPE-19 cells and HCMV-infected PMBCs showed upregulation of caspase-1, IL-1β, and IL-18 mRNAs at some time during HCMV infection from 10 min to 48 hr pi, although their temporal patterns of synthesis were cell-type specific. In contrast, HCMV-infected Jurkat cells showed upregulation of IL-1β mRNA at 10 min to 24 hr pi, but caspase-1 and IL-18 mRNAs were not upregulated at any time up to 48 hr pi. Similarly, HCMV-infected MRC-5 cells showed upregulation of IL-1β and IL-18 mRNAs at 24 to 48 hr pi, but caspase-1 mRNA was not upregulated at any time up to 48 hr pi.
Although IL-1β mRNA was upregulated in all cell types at some time following HCMV infection, concurrent expression of caspase-1 and IL-18 mRNAs was observed only in HCMV-infected ARPE-19 cells and HCMV-infected PBMCs suggesting HCMV-induced pyroptosis. Jurkat cells and MRC-5 cells infected with HCMV failed to show induction of all pyroptosis-related molecules. We conclude that caspase-1-dependent and caspase-1-independent IL-1β mRNA expression (and possibly pyroptosis) during productive (lytic) HCMV infection is cell-type specific.
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