Inhibition of Apoptosis in
            <i>Cryptosporidium parvum</i>
            -Infected Intestinal Epithelial Cells Is Dependent on Survivin

Liu, Jin; Enomoto, Shinichiro; Lancto, Cheryl A.; Abrahamsen, Mitchell S.; Rutherford, Mark S.

doi:10.1128/iai.00308-08

Cited by 48 publications

(54 citation statements)

References 68 publications

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“…The time points assayed (2, 6, 12, 24, 36, 48, and 72 hr) were predicted to be integral transitional states during in vitro parasite development based on our morphological assessment [25] (Figure 1) and other reports [30]. Transcripts were measured using four independent culture replicates.…”

Section: Discussionmentioning

confidence: 90%

The Cryptosporidium Parvum Transcriptome during In Vitro Development

Mauzy¹,

Enomoto²,

Lancto³

et al. 2012

PLoS ONE

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106

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Cryptosporidiosis is caused by an obligate intracellular parasite that has eluded global transcriptional or proteomic analysis of the intracellular developmental stages. The transcript abundance for 3,302 genes (87%) of the Cryptosporidium parvum protein coding genome was elucidated over a 72 hr infection within HCT8 cells using Real Time-PCR. The parasite had detectable transcription of all genes in vitro within at least one time point tested, and adjacent genes were not co-regulated. Five genes were not detected within the first 24 hr of infection, one containing two AP2 domains. The fewest genes detected were at 2 hr post infection, while 30% (985) of the genes have their highest expression at 48 and/or 72 hr. Nine expression clusters were formed over the entire 72 hr time course and indicate patterns of transcriptional increases at each of the 7 time points collected except 36 hr, including genes paralleling parasite 18S rRNA transcript levels. Clustering within only the first 24 hr of infection indicates spikes in expression at each of the 4 time points, a group paralleling 18S rRNA transcript levels, and a cluster with peaks at both 6 and 24 hr. All genes were classified into 18 functional categories, which were unequally distributed across clusters. Expression of metabolic, ribosomal and proteasome proteins did not parallel 18S rRNA levels indicating distinct biochemical profiles during developmental stage progression. Proteins involved in translation are over-represented at 6 hr, while structural proteins are over-represented at 12 hr. Standardization methods identified 107 genes with <80% at a single of its total expression at a single time point over 72 hr. This comprehensive transcriptome of the intracellular stages of C. parvum provides insight for understanding its complex development following parasitization of intestinal epithelial cells.

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Section: Discussionmentioning

confidence: 90%

The Cryptosporidium Parvum Transcriptome during In Vitro Development

Mauzy¹,

Enomoto²,

Lancto³

et al. 2012

PLoS ONE

Self Cite

106

116

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“…In the second, the viability of the cells surrounding the parasites, which is demonstrated by the absence of anti‐(active caspase‐3) labelling, would help to maintain the infection and provide nutrients in a similar manner as mammalian enterocytes infected with C. parvum (Liu et al . ).…”

Section: Discussionmentioning

confidence: 97%

Study of the distribution of active caspase‐3‐positive cells in turbot, Scophthalmus maximus (L.), enteromyxosis

Losada

Bermúdez

Faílde

et al. 2013

Journal of Fish Diseases

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Enteromyxosis caused by Enteromyxum scophthalmi is one of the parasitizations with a higher economic impact on turbot, Scophthalmus maximus (L.), aquaculture. This myxosporean produces severe catarrhal enteritis with abundant inflammatory infiltrates in the lamina propria-submucosa (LP), epithelial detachment and leucocyte depletion of the lymphohaematopoietic organs. Some advances made on the pathogenesis pointed to a role of apoptosis in the enteromyxosis. Therefore, the main aim of this work was to employ the TUNEL assay and the anti-(active caspase-3) immunohistochemical assay to detect apoptotic cells in both healthy and E. scophthalmi-infected turbot in order to establish the presence and distribution of apoptotic cells during development of the disease. More apoptotic cells located within the gastrointestinal epithelium were observed in the initial stages of the infection in E. scophthalmi-infected turbot compared with non-infected turbot. As the infection progressed, a higher degree of apoptosis occurred in the epithelium of folds heavily parasitized. In the severely infected turbot, apoptosis was also found among the leucocytes of the intestinal inflammatory infiltrates. Moreover, the number of active caspase-3-positive cells in the lymphohaematopoietic organs tended to increase with disease severity. In view of the results, increased apoptosis in the epithelium may favour the scaling that occurs during enteromyxosis and cell death of leucocytes in the intestinal LP, contributing to leucocyte depletion in severe cases.

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“…Between 24 h and 48 h, the merozoites appear and reinfect, resulting in an equal-part mixture of merozoites, trophozoites, and meronts. This was when survivin protects from apoptosis (28). This strong apoptosis inhibition can protect the cells even from staurosporine, yet depletion of survivin or XIAP results in high caspase activity, suggesting that Bcl-2 is not effective at this stage and/or that the caspases were not activated by the mitochondrial pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Cryptosporidium has apparently evolved countermeasures to keep the host cells in a survival mode. Indeed, the infected cells acquire resistance to various chemical agents that trigger apoptosis (6,28,33,35). Additionally, the host appears to be equipped with a second line of defense also involving apoptosis: uninfected bystander cells die due to FasL secreted from the infected cells (5,6,33,35).…”

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confidence: 99%

Biphasic Modulation of Apoptotic Pathways in Cryptosporidium parvum -Infected Human Intestinal Epithelial Cells

et al. 2009

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The impact of Cryptosporidium parvum infection on host cell gene expression was investigated by microarray analysis with an in vitro model using human ileocecal HCT-8 adenocarcinoma cells. We found changes in 333 (2.6%) transcripts at at least two of the five (6, 12, 24, 48, and 72 h) postinfection time points. Fifty-one of the regulated genes were associated with apoptosis and were grouped into five clusters based on their expression patterns. Early in infection (6 and 12 h), genes with antiapoptotic roles were upregulated and genes with apoptotic roles were downregulated. Later in infection (24, 48, and 72 h), proapoptotic genes were induced and antiapoptotic genes were downregulated, suggesting a biphasic regulation of apoptosis: antiapoptotic state early and moderately proapoptotic state late in infection. This transcriptional profile matched the actual occurrence of apoptosis in the infected cultures. Apoptosis was first detected at 12 h postinfection and increased to a plateau at 24 h, when 20% of infected cells showed nuclear condensation. In contrast, experimental silencing of Bcl-2 induced apoptosis in 50% of infected cells at 12 h postinfection. This resulted in a decrease in the infection rate and a reduction in the accumulation of meront-containing cells. To test the significance of the moderately proapoptotic state late in the infection, we inhibited apoptosis using pancaspase inhibitor Z-VAD-FMK. This treatment also affected the progression of C. parvum infection, as reinfection, normally seen late (24 h to 48 h), did not occur and accumulation of mature meronts was impaired. Control of host apoptosis is complex and crucial to the life of C. parvum. Apoptosis control has at least two components, early inhibition and late moderate promotion. For a successful infection, both aspects appear to be required.

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Inhibition of Apoptosis in Cryptosporidium parvum -Infected Intestinal Epithelial Cells Is Dependent on Survivin

Cited by 48 publications

References 68 publications

The Cryptosporidium Parvum Transcriptome during In Vitro Development

The Cryptosporidium Parvum Transcriptome during In Vitro Development

Study of the distribution of active caspase‐3‐positive cells in turbot, Scophthalmus maximus (L.), enteromyxosis

Biphasic Modulation of Apoptotic Pathways in Cryptosporidium parvum -Infected Human Intestinal Epithelial Cells

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