| Model |
Mmpa-MMPb/TIMPb expression patternc |
Functional data/associations |
Comments |
References |
| 1. In vitro |
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| T. gondii-infected THP-1 cells |
Mmp-2,-9, Timp-2↓, Mt1-mmp↑
proMMP-2, proMMP-9, TIMP-2↓
proMT1-MMP↑, actMT1-MMP↑ |
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MT1-MMP activation by T. gondii infection probably explains parasite dissemination and access to immune-priviledged sites. |
[347] |
| T. gondii-infected (macrophage-like) RAW 264.7 cells |
ActMMP-9↑ in infected supernatants
MT1-MMP↑ in T. gondii-infected cells
ADAM-10↑ in T. gondii-infected cells |
MMP inhibitor I → Abolished invasiveness of T. gondii-infected macrophages over 3D ECM
MMPs might facilitate the access of infected leukocytes to immune-privileged sites |
Increasing levels of MT1-MMP→ shedding of CD44→, a docking molecule for MMP-9 |
[345] |
| 2. In vivo |
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| Ileum tissue from T. gondii-infected mice |
Mmp-2,-9/MMP-2,-9↑ in small intestine
ActMMP-2↑ in small intestine
IL-23p19KO; mice
Mmp-2,-9/MMP-2,-9↓
No actMMP-2
→ Significantly reduced intestinal pathology |
MMP-2KO mice (compared to MMP-9KO and WT mice)
→ Protected against the development of intestinal immunopathology and early death; MMP-2 mediates immunopathology in T. gondii-infected ileitis.
Treatment with gelatinase inhibitors (doxycycline and MMPI RO28-2653)
→ Ameliorated intestinal pathology
Treatment with gelatinase inhibitors protects mice against T- gondii-induced immunopathology |
Selective blockage of gelatinoses may be a safe and effective strategy in prevention and treatment of intestinal inflammation |
[348] |
| Brain tissue from T. gondii-infected mice |
Mmp-8, -10 and TIMP-1↑ in brain
MMP-8↑ in brain infiltrating CD4+/CD8+ T cells
MMP-10↑ in brain infiltrating CD4+ T cells
TIMP-1↑ in CNS-resident astrocytes and in brain infiltrating CD4+/CD8+ T cells |
TIMP-1 deficient mice → Little morphological changes in tissue structure
→ ↑ CD4+ T cells in brain
→ Reduced parasite burden in brain
TIMP-1 is associated with inhibition of pathogen clearance without development of adverse pathology→ |
MMP-8 and –10 production by brain-infiltrating T cells implies a role for MMPs in brain tissue penetration; TIMP-1 is associated with inhibition of pathogen clearance |
[349] |
| 3. Clinical studies |
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| Serum from pregnant women with or without T. gondii infection vs. healthy non-pregnant women |
MMP-12 - > associated with ↑ elastin degradation products;
Pregnant women with toxoplasmosis > healthy pregnant women > healthy non-pregnant women |
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Interaction between MMP-12 and elastin in the serum of infected pregnant women suggests MMP-12 mediates damage to elastin and contributes to T. gondii-associated pathology during pregnancy |
350] |
↑↓: Increased or decreased levels; ADAM: A Disintegrin And Metalloprotease; actMMP: activated MMP; CNS: Central Nervous System; ECM: Extracellular Matrix; KO:
Knockout; MMP: Matrix Metalloproteinase; MT-MMP: Membrane-Type Matrix Metalloproteinase; TIMP: Tissue Inhibitor Of Metallopproteinases; 