Intracerebral Targets and Immunomodulation of Murine Listeria monocytogenes Meningoencephalitis

Abstract

In humans, infection with Listeria monocytogenes (L. monocytogenes) can severely affect the central nervous system (CNS). In the present study we have employed a murine model of CNS listeriosis to characterize the intracerebral distribution of L. monocytogenes. Following intracerebral application of a low dose of L. monocytogenes (serovar 1/2a, EGD strain) a severe fatal leptomeningitis, ventriculitis, and encephalitis developed. Listeria were detectable both intracellularly in different cell types of the CNS and extracellularly in the cerebrospinal fluid. Ultrastructural analysis revealed macrophages, granulocytes, plexus epithelial cells, ependymal cells, and neurons as target cells. An inflammatory reaction with macrophages and granulocytes developed in the brains of these animals but was not sufficient to prevent the fatal outcome of the disease. However, active immunization of mice prior to an intracerebral challenge infection significantly reduced the mortality. Immunized animals showed an early recruitment of a significant number of CD8+ and, to a lesser degree, CD4+ T cells within 24 hours p.i. as well as a strong activation of microglial cells and macrophages. These findings may provide an interesting model for studies on the pathogenesis of cerebral listeriosis.