NLRP3, NLRP12, and IFI16 Inflammasomes Induction and Caspase-1 Activation Triggered by Virulent HSV-1 Strains Are Associated With Severe Corneal Inflammatory Herpetic Disease

In this study, we used herpes simplex virus type 1 (HSV-1), the causative agent of corneal inflammatory herpetic disease, as a model pathogen to determine: (i) Whether and how the virulence of a virus affects the type and the activation level of the inflammasomes; and (ii) How triggering specific inflammasomes translates into protective or damaging inflammatory response. We showed that, in contrast to the less-virulent HSV-1 strains (RE, F, KOS and KOS63), corneal infection of B6 mice with the virulent HSV-1 strains (McKrae, 17 or KOS79): (i) Induced simultaneous high expression levels of the NLRP3, NLRP12 and IFI16 inflammasomes; (ii) Increased production of the biologically active Caspase-1 and pro-inflammatory cytokines IL-1 and IL-18; (iii) Heightened recruitment into the inflamed cornea of CD45highLy6C+Ly6G−F4/80+CD11b+CD11c− inflammatory monocytes and CD45highCD11b+F4/80−Ly6GhiLy6Cmed neutrophils; and (iv) This intensified inflammatory response was associated with a severe corneal herpetic disease, irrespective of the level of virus replication in the cornea. Similarly, in vitro infection of human corneal epithelial cells and THP‑1 cells with the virulent HSV-1 strains triggered a synchronized early expression of NLRP3, NLRP12 and IFI16, two hours post-infection, associated with formation of single and dense specks of the adapter molecule ASC in HSV(+) cells, but not in the neighboring bystander HSV(-) cells. This was associated with increased cleavages of Ca...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research