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Combinatory microarray and SuperSAGE analyses identify pairing-dependently transcribed genes in Schistosoma mansoni males, including follistatin

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Schistosoma mansoni

SUBMITTER: Silke Leutner

PROVIDER: E-GEOD-45696 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Combinatory microarray and SuperSAGE analyses identify pairing-dependently transcribed genes in Schistosoma mansoni males, such as follistatin [Microarray]

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Combinatory microarray and SuperSAGE analyses identify pairing-dependently transcribed genes in Schistosoma mansoni males, including follistatin [SuperSAGE]

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Project description:Schistosomes are blood-dwelling helminth parasites causing a debilitating disease in the tropics. Major challenges to control persist and vaccines would provide an additional tool, but finding protective antigens is not trivial. It's known that the self-cure response of Rhesus macaques targets proteins from the tegument, gut and esophagus, the last of which is the least investigated. Here we applied proteomics to characterise esophageal antigens with potential utility for vaccine development. This dataset was generated by partial reanalysis of our published MS-data (PXD014872; 10.1021/acs.jproteome.9b00531). Originally, we have shown that shotgun proteomics applied to dissected esophageal fragments identified 13 MEG proteins, eleven of which are uniquely located in the esophageal glands. Antigenic variation by alternative splicing of MEG proteins was confirmed together with a specialised machinery for protein glycosylation in the esophagus. Moreover some gastrodermal secretions were highly enriched in the gut, while others were more uniformly distributed, potentially as markers of lysosomal activity. In contrast to PXD014872, this reanalysis allowed semi-specific trypsin cleavage during database search. This has proven to increase N-terminal sequence coverage of proteins processed for signal peptide removal, including esophageal MEG proteins.

2024-06-20 | PXD037384 | Pride

CYP19A1 mediated sex hormone metabolism promotes severe disease outcome in SARS-CoV-2 infected male golden hamsters

Project description:Male sex belongs to one of the risk factors for severe COVID-19 outcome. However, underlying mechanisms that could affect sex dependent disease outcome are yet unknown. Here, we identified the CYP19A1 gene encoding for the testosterone-to-estradiol metabolizing enzyme CYP19A1 (alias aromatase) as a host factor that contributes to worsened disease outcome in male hamsters. SARS-CoV-2 infection increases CYP19A1 transcription most prominently in the lungs of male animals, which correlates with reduced circulating testosterone and increased circulating estradiol levels. Dysregulated sex hormone levels in male golden hamsters are associated with reduced lung function compared to females. Treatment of SARS-CoV-2 infected hamsters with letrozole, a clinically approved CYP19A1 inhibitor, supported recovery of dysregulated sex hormone levels and was associated with improved lung function in male but not female animals compared to placebo controls. Whole-lung transcriptome analysis in letrozole treated versus placebo treated control groups revealed key pathways associated with improved lung health in males. To seek translation of these findings into humans, we analyzed autopsy-derived lung samples of COVID-19 cases from three independent study sites. We found that CYP19A1 transcription and protein expression is strongly elevated in the lungs of men who died with COVID-19 as compared to females or non-COVID-19 controls. Our findings highlight the role of the lung as a yet unrecognized but critical organ involved in metabolic responses against respiratory virus infections. Furthermore, inhibition of CYP19A1 by the clinically approved drug letrozole may pose a new therapeutic strategy to reduce poor long-term COVID-19 outcome.

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Quantitative Proteomics of Enriched Esophageal and Gut Tissues from the Human Blood Fluke Schistosoma mansoni

Project description:Schistosomes are blood-dwelling helminth parasites causing a debilitating disease in the tropics. Major challenges to control persist and vaccines would provide an additional tool, but their development has been problematic. During the self-cure response of Rhesus macaques, antibodies target proteins from the tegument, gut and esophagus, the last of which is the least investigated. We developed a dissection technique that permitted comparative proteomics on the schistosome esophagus and gut. A shotgun analysis applied to male heads identified 13 MEG proteins, eleven of which were uniquely located in the esophageal glands. Antigenic variation by alternative splicing of MEG proteoforms was confirmed together with a specialised machinery for protein glycosylation in the esophagus. Moreover some gastrodermal secretions were highly enriched in the gut, while others were more uniformly distributed, potentially as markers of lysosomal activity. Collectively, our findings provide a more rational, better-oriented selection of schistosome vaccine candidates in the context of a proven model of protective immunity.

2019-12-11 | PXD014872 | Pride

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