Impact of caspase-1/11, -3, -7, or IL-1β/IL-18 deficiency on rabies virus-induced macrophage cell death and onset of disease

摘要: Rabies virus is a highly neurovirulent RNA virus, which causes about 59000 deaths in humans each year. Previously, we described macrophage cytotoxicity upon infection with rabies virus. Here examined the type of cell death and role specific caspases disease development two laboratory strains virus: Challenge Virus Standard strain-11 (CVS-11) neurotropic lethal for mice, while attenuated Evelyn-Rotnycki-Abelseth (ERA) strain has broader tropism, non-lethal been used as an oral vaccine animals. Infection Mf4/4 macrophages both led to caspase-1 activation IL-1β IL-18 production, well caspases-3, -7, -8, -9. Moreover, absence caspase-3, but not -11 or partially inhibited virus-induced bone marrow-derived macrophages. Intranasal inoculation CVS-11 mice deficient either -7 general brain similar wild-type mice. Deficiency on other hand, significantly delayed onset disease, did prevent final outcome. Interestingly, deficiency caspase-1/11, key executioner pyroptosis, aggravated severity caused by ERA whereas presented typical mild symptoms associated In conclusion, induces caspase-1- caspase-3-dependent death. vivo caspase-1/11 caspase-3 differently affect response virulent strain, respectively. Inflammatory seem control infection, aggravates infection.