Subcapsular sinus macrophages prevent CNS invasion on peripheral infection with a neurotropic virus

Lymphatic defence against neurotropic viruses Microorganisms that breach the body's external defences and enter the lymphatic system are liable to be captured by the lymph nodes, and recent work showed that a subset of macrophages found in the subcapsular sinus (SCS) of lymph nodes is critical for clearance of viruses from the lymph and for initiating antiviral humoral immune responses. Now a third function for SCS macrophages has been identified: the prevention of lymph-borne neurotropic viruses from infecting the CNS. Using vesicular stomatitis virus (VSV) as a model, Iannacone et al. showed that local depletion of SCS macrophages made mice injected subcutaneously with VSV more vulnerable to the virus via a mechanism dependent on type I interferon. VSV is a relative of rabies virus typically transmitted by insect bites, causing a fatal paralytic disease in some mammals. Combined with further experiments in mice lacking the IFN-I receptor, these findings suggest that SCS macrophages are crucial gatekeepers to the CNS that prevent fatal viral neuroinvasion upon peripheral infection.