Enhanced TLR3 responsiveness in hepatitis C virus resistant women from the Irish anti-D cohort

Natural resistance to infection is an overlooked outcome after hepatitis C virus (HCV) exposure. Between 1977 and 1979, 1,200 Rhesus D-negative Irish women were exposed to HCV-contaminated anti-D immuno-globulin. Here, we investigate why some individuals appear to resist infection despite exposure (exposed seronegative [ESN]). We screen HCV-resistant and-susceptible donors for anti-HCV adaptive immune re-sponses using ELISpots and VirScan to profile antibodies against all know human viruses. We perform stan-dardized ex vivo whole blood stimulation (TruCulture) assays with antiviral ligands and assess antiviral re-sponses using NanoString transcriptomics and Luminex proteomics. We describe an enhanced TLR3-type I interferon response in ESNs compared with seropositive women. We also identify increased inflammatory cytokine production in response to polyIC in ESNs compared with seropositive women. These enhanced re-sponses may have contributed to innate immune protection against HCV infection in our cohort.

Automated summary

This study found that some individuals can resist HCV infection despite exposure to the virus, possibly due to enhanced TLR3-type I interferon response and increased inflammatory cytokine production.