Affiliation:
1. Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden
2. Swedish Institute for Communicable Disease Control, 171 82 Stockholm, Sweden
Abstract
ABSTRACT
Disseminated toxoplasmosis in the central nervous system (CNS) is often accompanied by a lethal outcome. Studies with murine models of infection have focused on the role of systemic immunity in control of toxoplasmic encephalitis, while knowledge remains limited on the contributions of resident cells with immune functions in the CNS. In this study, the role of glial cells was addressed in the setting of recrudescent
Toxoplasma
infection in mice. Activated astrocytes and microglia were observed in the close vicinity of foci with replicating parasites
in situ
in the brain parenchyma.
Toxoplasma gondii
tachyzoites were allowed to infect primary microglia and astrocytes
in vitro
. Microglia were permissive to parasite replication, and infected microglia readily transmigrated across transwell membranes and cell monolayers. Thus, infected microglia, but not astrocytes, exhibited a hypermotility phenotype reminiscent of that recently described for infected dendritic cells. In contrast to gamma interferon-activated microglia,
Toxoplasma
-infected microglia did not upregulate major histocompatibility complex (MHC) class II molecules and the costimulatory molecule CD86. Yet
Toxoplasma
-infected microglia and astrocytes exhibited increased sensitivity to T cell-mediated killing, leading to rapid parasite transfer to effector T cells
in vitro
. We hypothesize that glial cells and T cells, besides their role in triggering antiparasite immunity, may also act as “Trojan horses,” paradoxically facilitating dissemination of
Toxoplasma
within the CNS. To our knowledge, this constitutes the first report of migratory activation of a resident CNS cell by an intracellular parasite.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
65 articles.
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