Critical Roles of NK and CD8+ T Cells in Central Nervous System Listeriosis

Abstract

Listeria monocytogenes (LM) causes a life-threatening infectious disease affecting the brain of humans and domestic animals. Unfortunately, no adequate murine models for CNS listeriosis exist. Using intraparenchymal injection, we have established a new murine model for CNS listeriosis. Injection of a small volume of bacterial suspension limits the bacteria to the brain parenchyma with no leakage into the ventricular system. This new method enabled us to investigate the progression of and recovery from listerial brain infection, revealing roles for both innate and adaptive immune cells in CNS listeriosis. In the early phase of CNS listeriosis, NK cell-derived IFN-γ is a critical cytokine in the limitation of bacterial growth by the host defense. During the later phase, CD8+ but not CD4+ T cells play a critical role and LM-specific CD8+ T cells kill LM-infected microglia. Thus, innate and adaptive immune responses combine to successfully eliminate bacteria from the brain.

Granzyme B Expression by CD8+ T Cells Is Required for the Development of Experimental Cerebral Malaria

“…Thus, our data provide evidence that modulation of CD8 + T cell function is a potential strategy to improve therapy against a wide range of diseases that occur in the brain. Given the proposed roles for CD8 + T cells in mediating or protecting against numerous brain-related diseases, such as viral encephalitis (58)(59)(60), toxoplasmosis (61,62), multiple sclerosis (63-65), brain tumors (29,31,66), and cerebral listeriosis (67)(68)(69), our data have implications that extend beyond ECM to other infectious diseases, cancer, and autoimmunity.…”

Brain dendritic cells: biology and pathology

“…This data suggest that DC were involved in the antigen uptake and processing responsible for T-cell activation [63]. Likewise, in another animal model of neonatal meningitis induced by intranasal infection with E. coli K1, a link between bacterial load/host survival and the expression of CD47 on DC was established.…”

CD8+ T Cells Primed in the Periphery Provide Time-Bound Immune-Surveillance to the Central Nervous System

“…The most severe outcomes in persons infected by L. monocytogenes occur when the bacteria invade the CNS, which can result in death (1). During primary infection, L. monocytogenes is controlled mainly by innate immunity (2,3).…”

“…During primary infection, L. monocytogenes is controlled mainly by innate immunity (2,3). In the brain, a primary infection with L. monocytogenes is controlled mainly by CD8 + T cells and NK cells, which develop after several days (1). Protection against a peripheral secondary infection is mediated mainly by CD8 + T cells through a mechanism that is IFN-g independent (4) but perforin (5) and TNF (6) dependent.…”