Division of Biomedical Sciences, University of California, Riverside, CA 92521, USA.
ASN Neuro. 2011 Jan 21;3(1):e00049. doi: 10.1042/AN20100027.
Chronic infection with the intracellular protozoan parasite Toxoplasma gondii leads to tissue remodelling in the brain and a continuous requirement for peripheral leucocyte migration within the CNS (central nervous system). In the present study, we investigate the role of MMPs (matrix metalloproteinases) and their inhibitors in T-cell migration into the infected brain. Increased expression of two key molecules, MMP-8 and MMP-10, along with their inhibitor, TIMP-1 (tissue inhibitor of metalloproteinases-1), was observed in the CNS following infection. Analysis of infiltrating lymphocytes demonstrated MMP-8 and -10 production by CD4+ and CD8+ T-cells. In addition, infiltrating T-cells and CNS resident astrocytes increased their expression of TIMP-1 following infection. TIMP-1-deficient mice had a decrease in perivascular accumulation of lymphocyte populations, yet an increase in the proportion of CD4+ T-cells that had trafficked into the CNS. This was accompanied by a reduction in parasite burden in the brain. Taken together, these findings demonstrate a role for MMPs and TIMP-1 in the trafficking of lymphocytes into the CNS during chronic infection in the brain.
弓形虫慢性感染会导致大脑组织重塑，并持续需要外周白细胞向中枢神经系统（CNS）迁移。在本研究中，我们研究了 MMP（基质金属蛋白酶）及其抑制剂在 T 细胞向感染大脑迁移中的作用。感染后，中枢神经系统中观察到两种关键分子 MMP-8 和 MMP-10 及其抑制剂 TIMP-1（金属蛋白酶组织抑制剂-1）的表达增加。对浸润淋巴细胞的分析表明，CD4+和 CD8+T 细胞产生 MMP-8 和 -10。此外，感染后浸润的 T 细胞和中枢神经系统固有星形胶质细胞增加了 TIMP-1 的表达。TIMP-1 缺陷小鼠的血管周围淋巴细胞群积聚减少，但已进入中枢神经系统的 CD4+T 细胞比例增加。这伴随着大脑中寄生虫负担的减少。总之，这些发现表明 MMP 和 TIMP-1 在慢性感染期间淋巴细胞向中枢神经系统迁移中发挥作用。
