Model Mmpa-MMPb/TIMPb expression patternc Functional data/associations Comments References
1. In vitro        
T. gondii-infected THP-1 cells Mmp-2,-9, Timp-2↓, Mt1-mmp↑
proMMP-2, proMMP-9, TIMP-2↓
proMT1-MMP↑, actMT1-MMP↑
  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        
Ileum tissue from T. gondii-infected mice Mmp-2,-9/MMP-2,-9↑ in small intestine
ActMMP-2↑ in small intestine
IL-23p19KO; mice
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        
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
  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; aMmp/Timp refers to mRNAs; bMMP/TIMP refers to proteins. WT: Wild Type.
Table 15: Expression and function of MMPs/TIMPs/ADAMs in toxoplasmosis (T. gondii infection) (acc. to Geurts et al. [346]; with own modification).