Infect Immun. 2011 May 31. [Epub ahead of print]
Migratory activation of primary cortical microglia upon infection with Toxoplasma gondii
Dellacasa-Lindberg I, Fuks JM, Arrighi RB, Lambert H, Wallin RP, Chambers BJ, Barragan A.
SourceCenter for Infectious Medicine, Dept. of Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden.
Disseminated Toxoplasmosis in the central nervous system (CNS) is often accompanied by lethal outcome. Studies in murine models of infection have focused on the role of systemic immunity for control of toxoplasmic encephalitis while knowledge remains limited on the contribution of resident cells with immune functions in the CNS. Here, the role of glia cells was addressed in the setting of recrudescent Toxoplasma infection in mice. Activated astrocytes and microglia were observed in 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 interferon γ-activated microglia, Toxoplasma-infected microglia did not upregulate MHC class II and the co-stimulatory 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 glia and T cells, besides their role in triggering anti-parasite 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.
PMID:21628522[PubMed - as supplied by publisher]