Analysis of Behavior and Trafficking of Dendritic Cells within the Brain during Toxoplasmic Encephalitis

PLoS Pathogens

Brendon Ricart¹  Daniel A. Hammer¹  Tajie H. Harris²  Daniel Manzoni De Almeida²  Beena John²  Beth Gregg²  Elia D. Tait Wojno²  Louise M. Randall²  David A. Christian²  Christopher A. Hunter²  Wolfgang Weninger³ 

[1] Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America;Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America;The Centenary Institute for Cancer Medicine and Cell Biology, Newtown, Australia

关键词: T cells;    Central nervous system;    Chemokines;    Parasitic diseases;    Microglial cells;    Spleen;    Antigen-presenting cells;    Integrins;   

DOI  :  10.1371/journal.ppat.1002246

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Under normal conditions the immune system has limited access to the brain; however, during toxoplasmic encephalitis (TE), large numbers of T cells and APCs accumulate within this site. A combination of real time imaging, transgenic reporter mice, and recombinant parasites allowed a comprehensive analysis of CD11c+ cells during TE. These studies reveal that the CNS CD11c+ cells consist of a mixture of microglia and dendritic cells (DCs) with distinct behavior associated with their ability to interact with parasites or effector T cells. The CNS DCs upregulated several chemokine receptors during TE, but none of these individual receptors tested was required for migration of DCs into the brain. However, this process was pertussis toxin sensitive and dependent on the integrin LFA-1, suggesting that the synergistic effect of signaling through multiple chemokine receptors, possibly leading to changes in the affinity of LFA-1, is involved in the recruitment/retention of DCs to the CNS and thus provides new insights into how the immune system accesses this unique site.

【 授权许可】

CC BY