title: T-cell production of matrix metalloproteinases and inhibition of parasite clearance by TIMP-1 during chronic Toxoplasma infection in the brain.
abstract: 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.
authors: Division of Biomedical Sciences, University of California, Riverside, CA 92521, USA.
authors: Robin T
authors: RT
authors: Clark
authors: J Philip
authors: JP
authors: Nance
authors: Shahani
authors: S
authors: Noor
authors: Emma H
authors: EH
authors: Wilson
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000469:parasitology; D001921:Brain / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D015704:CD4 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002364:Caseins; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000172:deficiency / Q000378:metabolism*; D014123:Toxoplasmosis / Q000473:pathology* / Q000503:physiopathology; D015854:Up-Regulation / Q000235:genetics
chemical_list: D015704:CD4 Antigens; D002364:Caseins; D016207:Cytokines; D010446:Peptide Fragments; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; C056550:KNQDK peptide; D020782:Matrix Metalloproteinases