Infection drives long-term meningeal engraftment by inflammatory monocytes that impair central nervous system immunity [II]

Tissue-resident macrophages have an embryonic origin, but are replenished under steady state conditions in some tissues by blood monocytes that can adopt genotypic and phenotypic features of the residents. However, little is known about the residency and functional properties of infiltrating macrophages after an inflammatory challenge. The meninges of the central nervous system (CNS) are populated by a dense network of specialized macrophages that act as resident immune sentinels. Here we show that following lymphocytic choriomeningitis virus infection resident meningeal macrophages become activated by innate inflammatory cytokines, acquire viral antigen, and interact directly with infiltrating cytotoxic T lymphocytes (CTL), which leads to their depletion. Concurrently, the meninges are heavily infiltrated by peripherally-derived inflammatory monocytes that engraft the meningeal niche and remain in situ for months after viral clearance. This engraftment leads to phenotypic and functional changes in the pool of resident meningeal macrophages that depends in part on IFNγ signaling. These changes include loss of bacterial and immunoregulatory sensors that impede subsequent CNS immune reactions. Collectively, these data indicate that peripheral monocytes can engraft the meninges after an inflammatory challenge, imprinting the compartment with long-term defects in immune function. Transcript profiles for 8x20-25 separate mice representing CD206+ MHC-II+ or CD206+ MHC-II- macrophages of the meninges at Day 30 post PBS-treatment (n=4 pools of 20-25 mice) or LCMV infection (n=4 pools of 20-25 mice).