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A. Bergua, N. Kittan, S. Haupt, N. Dornhauser, K. Korn, B. Schmidt; Selective Innate Immunodeficiency in Patients With Severe Herpesvirus Retinitis?. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5166.
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The first-line recognition of viruses and virus-infected cells is mediated via the innate immune system. An important component are plasmayctoid dendritic cells (PDC), which have been identified as major producers of type I interferons (IFN). Severe viral infections in non-immunosuppressed patients may result from selective defects in the innate recognition of these viruses.
Peripheral blood mononuclear cells (PBMC) were isolated from EDTA-containing blood of healthy controls or patients with viral retinitis. PDC were purified from the PBMC population using a BDCA-4 Cell Isolation Kit. PDC were then challenged with herpes simplex type 1 (HSV-1), CpG-A (ODN 2336, Coley Pharmaceutical Group), and a synthetic TLR7 agonist (S27609, 3M Pharmaceuticals). Supernatants were analysed for the presence of IFN-alpha.
So far, 5 healthy controls and 3 patients have been included. One patient had experienced HSV-1 encephalitis, followed by HSV-1 retinitis 12 months later. The second patient had suffered from fulminant necrotizing uveitis caused by HSV-1, and the third patient experienced a varicella zoster virus (VZV)-associated retinitis. PDC of the control individuals readily responded to all stimuli with secretion of high IFN-α levels. In contrast, PDC obtained from the patients with HSV-1 retinitis did not respond to HSV challenge. PDC derived from the patient with VZV-retinitis produced IFN-alpha in response to HSV, but not CpG.
Non-immunosuppressed patients who suffer from fulminant infection with HSV show defects in the induction of IFN-alpha production by PDC. Current studies are directed at identifying the block in IFN signaling.
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