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Antibody profile in patients with mild and severe leptospirosis

ABSTRACT: Leptospirosis is zoonotic disease of global importance, with over a million cases andnearly 60,000 deaths annually. Symptomatic disease presentation ranges from a mildfebrile disease with non-specific symptoms to severe forms, characterized by multi-organ failure, lung hemorrhage, and death. Factors governing severe outcomes remainunclear, but the host immune response likely plays an important role. In the presentstudy, we applied high throughput techniques to identify the antibody profiles ofpatients with severe and mild leptospirosis. We discovered a limited number ofimmunodominant antigens, specific to patients. Surprisingly, we found the antibodyrepertoire varies in patients with different clinical outcomes and hypothesized thatpatients with mild symptoms were protected from severe disease due to pre-existingantibodies, while the profile of patients with severe outcomes was representative of afirst exposure. These findings represent a substantial step forward in the knowledge ofthe humoral immune response to Leptospira infection, and we have identified newtargets for vaccine and diagnostic test development.

ORGANISM(S): Leptospira interrogans serovar Copenhageni Homo sapiens

PROVIDER: GSE86630 | GEO | 2016/09/10

SECONDARY ACCESSION(S): PRJNA342469

REPOSITORIES: GEO

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Project description:Leptospirosis, an emerging zoonotic disease with worldwide distribution, is caused by spirochetes belonging to the genus Leptospira. More than 500,000 cases of severe leptospirosis are reported annually, with .10% of these being fatal. Leptospires can survive for weeks in suitably moist conditions before encountering a new host. Reservoir hosts, typically rodents, exhibit little to no signs of disease but shed large numbers of organisms in their urine. Transmission occurs when mucosal surfaces or abraded skin come into contact with infected urine or urine-contaminated water or soil. In humans, leptospires can cause a variety of clinical manifestations, ranging from asymptomatic or mild fever to severe icteric (Weil’s) disease and pulmonary haemorrhage. Currently, little is known about how Leptospira persist within a reservoir host. Prior in vitro studies have suggested that leptospires alter their transcriptomic and proteomic profiles in response to environmental signals encountered during mammalian infection. However, no study has examined gene expression by leptospires within a mammalian host-adapted state. To obtain a more faithful representation of how leptospires respond to host-derived signals, we used RNA-Seq to compare the transcriptome of L. interrogans cultivated within dialysis membrane chambers (DMCs) implanted into the peritoneal cavities of rats with that of organisms grown in vitro. In addition to determining the relative expression levels of ‘‘core’’ housekeeping genes under both growth conditions, we identified 166 genes that are differentially-expressed by L. interrogans in vivo. Our analyses highlight physiological aspects of host adaptation by leptospires relating to heme uptake and utilization. We also identified 11 novel non-coding transcripts that are candidate small regulatory RNAs. The DMC model provides a facile system for studying the transcriptional and antigenic changes associated with mammalian host-adaption, selection of targets for mutagenesis, and the identification of previously unrecognized virulence determinants. Transcriptome analysis of L. interrogans Copenhageni FIOCRUZ L1-130 using RNA from 2 different conditions using RNA-seq. Also, the reproducibility and robustness of data is ensured by three biological replicates from each condition.

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Antibody profile in patients with mild and severe leptospirosis

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