Antigen depots

The effects of type 1 interferon (IFN), which is normally produced by mammalian cells following viral infection, are unexpectedly inhibited in specialized immune cells during vesicular stomatitis virus (VSV) infection, according to a report published in Nature Immunology. This finding could have implications for vaccine design. Usp18 is a host protein that dampens type 1 interferon signaling. Karl Sebastian Lang and colleagues show that specialized cells in the spleen, called metallophilic macrophages, express high amounts of Usp18. By inhibiting IFN, Usp18 allows viral replication in these cells, which is necessary for the generation of neutralizing antibodies and antiviral T cells. Interfering with the ‘antigen depot’ function of these cells leads to failure of the adaptive immune responses against VSV and viral dissemination to the central nervous system. Targeting vaccines to metallophilic macrophages could increase the chances of generating a protective adaptive immune response.