Dynamic imaging of T cell-parasite interactions in the brains of mice chronically infected with Toxoplasma gondii.
The intracellular parasite Toxoplasma gondii can establish persistent infection in the brain of a mammalian host, a standoff that involves the active participation of host CD8 T cells to control infection. CD8 T cells generally protect against intracellular pathogens by local delivery of effector molecules upon recognition of specific pathogen Ags on invaded host cells. However, the interactions between CD8 T cells, T. gondii, and APCs in the brain have not yet been examined. In this study we have used a mouse infection model in conjunction with two-photon microscopy of living brain tissue and confocal microscopy of fixed brain sections to examine the interactions between CD8 T cells, parasites, and APCs from chronically infected mice. We found that Ag-specific CD8 T cells were recruited to the brains of infected mice and persisted there in the presence of ongoing Ag recognition. Cerebral CD8 T cells made transient contacts with granuloma-like structures containing parasites and with individual CD11b(+) APCs, including some that did not contain parasites. In contrast, T cells ignored intact Ag-bearing cysts and did not contact astrocytes or neurons, including neurons containing parasites or cysts. Our data represent the first direct observation of the dynamics of T cell-parasite interactions within living tissue and provide a new perspective for understanding immune responses to persistent pathogens in the brain.
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Marie
M
Schaeffer
Seong-Ji
SJ
Han
Tatyana
T
Chtanova
Giel G
GG
van Dooren
Paul
P
Herzmark
Ying
Y
Chen
Badrinath
B
Roysam
Boris
B
Striepen
Ellen A
EA
Robey
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001921:Brain / Q000276:immunology* / Q000469:parasitology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D005434:Flow Cytometry; D006790:Host-Parasite Interactions / Q000276:immunology*; D007091:Image Processing, Computer-Assisted; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D014124:Toxoplasmosis, Animal / Q000276:immunology*; D016781:Toxoplasmosis, Cerebral / Q000276:immunology*