Glycosylphosphatidylinositols of Toxoplasma gondii induce matrix metalloproteinase-9 production and degradation of galectin-3

Niehus, Sebastian; Elass, Elisabeth; Coddeville, Bernadette; Guérardel, Yann; Schwarz, Ralph Τ.; Debierre‐Grockiego, Françoise

doi:10.1016/j.imbio.2011.08.001

Cited by 8 publications

(6 citation statements)

References 19 publications

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“…Opposite to what Bauche [204] observed, Seipel [205] observed that T. gondii infection increased the secretion of an active MMP-9 form [214, 215]. Confirming what Seipel [205] reported, recent research has shown that T. gondii GPIs induce the production of MMP-9 in human macrophage-like THP-1 cells via a TLR2/4 in a TNF α -dependent mechanism [206]. …”

Section: Intracellular Protozoamentioning

confidence: 79%

Host-Parasite Interaction: Parasite-Derived and -Induced Proteases That Degrade Human Extracellular Matrix

Piña-Vázquez

Reyes-López

Ortiz-Estrada

et al. 2012

Journal of Parasitology Research

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Parasitic protozoa are among the most important pathogens worldwide. Diseases such as malaria, leishmaniasis, amoebiasis, giardiasis, trichomoniasis, and trypanosomiasis affect millions of people. Humans are constantly threatened by infections caused by these pathogens. Parasites engage a plethora of surface and secreted molecules to attach to and enter mammalian cells. The secretion of lytic enzymes by parasites into host organs mediates critical interactions because of the invasion and destruction of interstitial tissues, enabling parasite migration to other sites within the hosts. Extracellular matrix is a complex, cross-linked structure that holds cells together in an organized assembly and that forms the basement membrane lining (basal lamina). The extracellular matrix represents a major barrier to parasites. Therefore, the evolution of mechanisms for connective-tissue degradation may be of great importance for parasite survival. Recent advances have been achieved in our understanding of the biochemistry and molecular biology of proteases from parasitic protozoa. The focus of this paper is to discuss the role of protozoan parasitic proteases in the degradation of host ECM proteins and the participation of these molecules as virulence factors. We divide the paper into two sections, extracellular and intracellular protozoa.

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Section: Intracellular Protozoamentioning

confidence: 79%

Host-Parasite Interaction: Parasite-Derived and -Induced Proteases That Degrade Human Extracellular Matrix

Piña-Vázquez

Reyes-López

Ortiz-Estrada

et al. 2012

Journal of Parasitology Research

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“…However, a combined involvement of other TLRs was reported in the development of T. gondii infection in mice as well as in humans [ 25 , 26 ]. Some participation of both TLR2 and TLR4 in triggering an immune response after T. gondii infection was observed in human macrophages, while a sort of cooperation among TLR7 TLR9, and TLR11 was shown in mice [ 8 , 25 , 26 ]. The outcomes of our study may suggest a contribution of all the analyzed polymorphic sites in the immune response against T. gondii .…”

Section: Discussionmentioning

confidence: 99%

Possible role of TLR4 and TLR9 SNPs in protection against congenital toxoplasmosis

Wujcicka

Gaj

Wilczyński

et al. 2015

Eur J Clin Microbiol Infect Dis

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The purpose of this investigation was the determination of the distribution of genotypes at single nucleotide polymorphisms (SNPs) of the toll-like receptor 4 (TLR4) and the toll-like receptor 9 (TLR9) in fetuses and newborns congenitally infected with Toxoplasma gondii and the identification of genetic changes predisposing to infection development. The study involved 20 fetuses and newborns with congenital toxoplasmosis and 50 uninfected controls. The levels of IgG and IgM antibodies against T. gondii, as well as IgG avidity, were estimated by enzyme-linked fluorescent assay (ELFA) tests. T. gondii DNA loads in amniotic fluids were assayed by the real-time (RT) quantitative polymerase chain reaction (Q PCR) technique for parasitic B1 gene. TLR4 and TLR9 SNPs were identified using a self-designed multiplex nested PCR-restriction fragment length polymorphism (RFLP) assay. Randomly selected genotypes at SNPs were confirmed by sequencing. All the genotypes were tested for Hardy–Weinberg equilibrium and TLR4 genotypes were analyzed for linkage disequilibrium. A correlation was studied between the genotypes or haplotypes and the development of congenital toxoplasmosis using a logistic regression model. Single SNP analysis showed no statistically significant differences in the distribution of distinct genotypes at the analyzed TLR4 and TLR9 SNPs between T. gondii-infected fetuses and newborns and the controls. Taking into account the prevalence of alleles residing within polymorphic sites, similar prevalence rates were observed in both of the studied groups. The multiple SNP analysis indicated GTG variants at the TLR4 and TLR9 SNPs to be significantly less frequent in offspring with congenital toxoplasmosis than in uninfected offspring (p ≤ 0.0001). TLR4 and TLR9 SNPs seem to be involved in protection against congenital toxoplasmosis.

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“…We showed further that the GPIs of the PTG strain activate TLR4 in a NF-κB CHO/CD14 reporter cell line with comparable magnitudes to those of the RH strain, suggesting that the cytokine induction is due to identical signaling events initiated by macrophage TLRs [36]. The GPIs of both strains have been also shown to stimulate the synthesis of matrix metalloproteinase (MMP)-9 by macrophages in a TNF-α-dependent manner and to degrade extracellular galectin-3 [52]. The GPI-induced degradation of galectin-3 by MMP-9 could have a regulatory function on TLR-signaling in response to GPIs [52].…”

Section: Discussionmentioning

confidence: 73%

“…The GPIs of both strains have been also shown to stimulate the synthesis of matrix metalloproteinase (MMP)-9 by macrophages in a TNF-α-dependent manner and to degrade extracellular galectin-3 [52]. The GPI-induced degradation of galectin-3 by MMP-9 could have a regulatory function on TLR-signaling in response to GPIs [52]. We conclude that GPIs of RH and PTG strains activate similar signaling events in macrophages due to similar structures.…”

Section: Discussionmentioning

confidence: 79%

Virulent and Avirulent Strains of Toxoplasma gondii Which Differ in Their Glycosylphosphatidylinositol Content Induce Similar Biological Functions in Macrophages

et al. 2014

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Glycosylphosphatidylinositols (GPIs) from several protozoan parasites are thought to elicit a detrimental stimulation of the host innate immune system aside their main function to anchor surface proteins. Here we analyzed the GPI biosynthesis of an avirulent Toxoplasma gondii type 2 strain (PTG) by metabolic radioactive labeling. We determined the biological function of individual GPI species in the PTG strain in comparison with previously characterized GPI-anchors of a virulent strain (RH). The GPI intermediates of both strains were structurally similar, however the abundance of two of six GPI intermediates was significantly reduced in the PTG strain. The side-by-side comparison of GPI-anchor content revealed that the PTG strain had only ∼34% of the protein-free GPIs as well as ∼70% of the GPI-anchored proteins with significantly lower rates of protein N-glycosylation compared to the RH strain. All mature GPIs from both strains induced comparable secretion levels of TNF-α and IL-12p40, and initiated TLR4/MyD88-dependent NF-κBp65 activation in macrophages. Taken together, these results demonstrate that PTG and RH strains differ in their GPI biosynthesis and possess significantly different GPI-anchor content, while individual GPI species of both strains induce similar biological functions in macrophages.

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Glycosylphosphatidylinositols of Toxoplasma gondii induce matrix metalloproteinase-9 production and degradation of galectin-3

Cited by 8 publications

References 19 publications

Host-Parasite Interaction: Parasite-Derived and -Induced Proteases That Degrade Human Extracellular Matrix

Host-Parasite Interaction: Parasite-Derived and -Induced Proteases That Degrade Human Extracellular Matrix

Possible role of TLR4 and TLR9 SNPs in protection against congenital toxoplasmosis

Virulent and Avirulent Strains of Toxoplasma gondii Which Differ in Their Glycosylphosphatidylinositol Content Induce Similar Biological Functions in Macrophages

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