J Immunol. 2009 May 15;182(10):6379-93
Dynamic imaging of T cell-parasite interactions in the brains of mice chronically infected with Toxoplasma gondii
Schaeffer M, Han SJ, Chtanova T, van Dooren GG, Herzmark P, Chen Y, Roysam B, Striepen B, Robey EA.
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
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.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
PMID: 19414791 [PubMed - in process]