Protozoan parasites: programmed cell death as a mechanism of parasitism

Bruchhaus, Iris; Roeder, Thomas; Rennenberg, Annika; Heussler, Volker

doi:10.1016/j.pt.2007.06.004

Cited by 83 publications

(75 citation statements)

References 73 publications

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“…After centrifugation, soluble proteins were separated by standard sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to nitrocellulose by semidry blotting. Equal loading of each lane was confirmed by staining with Ponceau S. Prior to the immunodetection of specific proteins, nonspecific binding sites had been blocked by using 5% dry skimmed milk-0.2% Tween 20-0.02% NaN 3 Subcellular distribution of cytochrome c. Cytochrome c was morphologically detected by immunofluorescence staining and confocal microscopy. For this purpose, infected and uninfected HeLa-Fas cells were fixed with 4% paraformaldehyde, quenched, and permeabilized with saponin as described above.…”

Section: Methodsmentioning

confidence: 99%

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Fas/CD95-Mediated Apoptosis of Type II Cells Is Blocked byToxoplasma gondiiPrimarily via Interference with the Mitochondrial Amplification Loop

et al. 2008

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The intracellular protozoan Toxoplasma gondii induces persistent infections in various hosts and is an important opportunistic pathogen of humans with immature or deficient immune responses. The ability to survive intracellularly largely depends on the blocking of different proapoptotic signaling cascades of its host cell. Fas/CD95 triggers an apoptotic cascade that is crucial for immunity and the outcome of infectious diseases. We have determined the mechanism by which T. gondii counteracts death receptor-mediated cell death in type II cells that transduce Fas/CD95 ligation via caspase 8-mediated activation of the mitochondrial amplification loop. The results showed that infection with T. gondii significantly reduced Fas/CD95-triggered apoptosis in HeLa cells by inhibiting the activities of initiator caspases 8 and 9 and effector caspase 3/7. Parasitic infection dose dependently diminished cleavage of caspase 8, the BH3-only protein Bid, and the downstream caspases 9 and 3. Importantly, interference with Fas/CD95-triggered caspase 8 and caspase 3/7 activities after parasitic infection was largely dependent on the presence of caspase 9. Within the mitochondrial amplification loop, T. gondii significantly inhibited the Fas/CD95-triggered release of cytochrome c into the host cell cytosol. These results indicate that T. gondii inhibits Fas/CD95-mediated apoptosis in type II cells primarily by decreasing the apoptogenic function of mitochondria.

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Section: Methodsmentioning

confidence: 99%

“…After infection, T. gondii renders host cells resistant to apoptosis induced by various proapoptotic stimuli (3,21,31). This is assumed to be a crucial adaptation of the parasite to its lifestyle that allows sustained intracellular survival and establishing of long-term persistence within its hosts, including up to 30% of humans worldwide.…”

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confidence: 99%

Fas/CD95-Mediated Apoptosis of Type II Cells Is Blocked byToxoplasma gondiiPrimarily via Interference with the Mitochondrial Amplification Loop

et al. 2008

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“…1 Both authors contributed equally to this work. 2 To whom correspondence should be addressed: 5 Science Drive 2, Singapore 117597.…”

Section: The Nucleotide Sequence(s) Reported In This Paper Has Been Smentioning

confidence: 99%

“…Several stereotypic apoptotic morphological markers similar to those observed in apoptotic metazoan cells have been described in human parasitic protozoa such as Leishmania amazonensis, Leishmania donovani, Trypanosoma cruzi, Trypanosoma brucei, Trypanosoma rhodesiense, Plasmodium falciparum, and Blastocystis (1,2). Despite a wealth of information on the organelles and cytochemical features involved in protozoan PCD, there is a scarcity of information on PCD 3 -related molecular mediators.…”

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confidence: 99%

Blastocystis Legumain Is Localized on the Cell Surface, and Specific Inhibition of Its Activity Implicates a Pro-survival Role for the Enzyme

Yin

Texier

et al. 2010

Journal of Biological Chemistry

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Programmed cell death (PCD) is crucial for cellular growth and development in multicellular organisms. Although distinct PCD features have been described for unicellular eukaryotes, homology searches have failed to reveal clear PCD-related orthologues among these organisms. Our previous studies revealed that a surface-reactive monoclonal antibody (mAb) 1D5 could induce multiple PCD pathways in the protozoan Blastocystis. In this study, we identified, by two-dimensional gel electrophoresis and mass spectrometry, the target of mAb 1D5 as a surface-localized legumain, an asparagine endopeptidase that is usually found in lysosomal/acidic compartments of other organisms. Recombinant Blastocystis legumain displayed biphasic pH optima in substrate assays, with peaks at pH 4 and 7.5. Activity of Blastocystis legumain was greatly inhibited by the legumain-specific inhibitor carbobenzyloxy-Ala-Ala-AAsn-epoxycarboxylate ethyl ester (APE-RR) (where AAsn is aza-asparagine) and moderately inhibited by mAb 1D5, cystatin, and caspase-1 inhibitor. Interestingly, inhibition of legumain activity induced PCD in Blastocystis, observed by increased externalization of phosphatidylserine residues and in situ DNA fragmentation. In contrast to plants, in which legumains have been shown to play a pro-death role, legumain appears to display a pro-survival role in Blastocystis.Programmed cell death in the unicellular protozoa is now accepted as a well established phenomenon. Several stereotypic apoptotic morphological markers similar to those observed in apoptotic metazoan cells have been described in human parasitic protozoa such as Leishmania amazonensis, Leishmania donovani, Trypanosoma cruzi, Trypanosoma brucei, Trypanosoma rhodesiense, Plasmodium falciparum, and Blastocystis (1, 2). Despite a wealth of information on the organelles and cytochemical features involved in protozoan PCD, there is a scarcity of information on PCD 3 -related molecular mediators. Our earlier studies showed that Blastocystis undergoes programmed cell death when exposed to the surface-reactive monoclonal antibody mAb 1D5 with typical features of apoptotic cells (3, 4). mAb 1D5 was shown to target a 30-kDa protein found on the plasma membrane of Blastocystis (5-7). This protein is functionally important, but not all cells within a clonal population would be susceptible to the cytotoxic effects of mAb 1D5 (6). These results suggest that this protein may have multiple localizations and is potentially important for cell survival. In this study, an asparaginyl cysteine protease legumain was identified as the mAb 1D5 targeting protein. Legumain is a recently described lysosomal protease, well conserved and present in plants, mammals, helminth worms, and the protozoan Trichomonas vaginalis (8 -12). The active site of legumain contains the catalytic dyad His-Gly-spacer-Ala-Cys, a characteristic shared with caspases, aspartyl cysteine proteases important as molecular mediators of apoptosis cascades (13). Legumains have specificity for the hydrolysis of bonds on the carb...

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“…Na saliva de Lu. longipalpis também se encontrou adenosina, que possui funções como: retardar efeitos apoptóticos em células T, efeitos de vasodilatação e agregação plaquetária (Wanderley et al, 2006;Bruchhaus et al, 2007). Finalmente, o que se observa é que a saliva do vetor possui um complexo enzimático muito eficiente para escapar das propriedades hemostáticas do hospedeiro.…”

Section: Saliva Do Vetorunclassified

Infecção experimental de camundongos C57BL/6 por L.(L.) amazonensis na presença de saliva de Lu. longipalpis: estudo da relação parasito-hospedeiro com ênfase a parâmetros da imunidade

Pernichelli¹

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Protozoan parasites: programmed cell death as a mechanism of parasitism

Cited by 83 publications

References 73 publications

Fas/CD95-Mediated Apoptosis of Type II Cells Is Blocked byToxoplasma gondiiPrimarily via Interference with the Mitochondrial Amplification Loop

Fas/CD95-Mediated Apoptosis of Type II Cells Is Blocked byToxoplasma gondiiPrimarily via Interference with the Mitochondrial Amplification Loop

Blastocystis Legumain Is Localized on the Cell Surface, and Specific Inhibition of Its Activity Implicates a Pro-survival Role for the Enzyme

Infecção experimental de camundongos C57BL/6 por L.(L.) amazonensis na presença de saliva de Lu. longipalpis: estudo da relação parasito-hospedeiro com ênfase a parâmetros da imunidade

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