Infection control in the brain and the eye

The Central Nervous System (CNS), comprising the brain and the eye, is considered to have a 'privileged' mechanism for dealing with immunological challenge (immune privilege, IP). CNS IP has been revealed through experiments using foreign protein antigens and cell and tissue alloantigens (grafts), but evidence for a role for IP in modulating host-pathogen interactions in the CNS is limited. However, the low frequency of CNS infection in the face of widespread systemic exposure to CNS-tropic infectious agents, together with the high incidence of CNS infection in immunocompromised individuals, suggests that in healthy individuals, the CNS has tightly controlled regulatory mechanisms to protect against infectious agents. Although the naïve healthy brain and retina parenchyma largely lack adaptive immune cells, their border tissues (meninges, uveal tract) contain a full complement of resident immune cells, including CNS-specific regulatory T cells (Tregs), which have a fundamental role in controlling infection in the brain parenchyma. Tregs also underpin ocular IP, particularly of the neural retina. Recent studies report that Tregs are transcriptionally 'customised' to the CNS and function at a distance; that is, are located in niches/hubs around the venous sinuses of the border tissues. T cells resident in the uveal tract probably play a similar role. We propose that Tregs are key drivers of CNS IP and do so by promoting latency of infectious agents.