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Multi-omics profiling of the host response to Leptospira infection in human PBMCs

ABSTRACT: This study provides a comprehensive multi-omics analysis of the human host response during acute leptospirosis. We performed integrated transcriptomic and proteomic profiling of peripheral blood mononuclear cells (PBMCs) from clinically confirmed leptospirosis patients and healthy controls. Our analysis reveals widespread dysregulation of host pathways, including potent activation of TNF-alpha/NF-kappaB signaling, interferon responses, and inflammatory and immunometabolic pathways. We identified a conserved core host response signature, validated key immune mediators in an ex vivo whole-blood infection model, and pinpointed a multi-protein signature associated with the disease. This dataset offers a valuable resource for understanding the molecular mechanisms of host-pathogen interactions in leptospirosis and identifies potential biomarkers and therapeutic targets.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Blood

DISEASE(S): Leptospirosis

SUBMITTER: Faisal Syed M

LAB HEAD: Syed M. Faisal

PROVIDER: PXD070502 | Pride | 2026-05-13

REPOSITORIES: Pride

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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.

			Action	DRS
	Ctrl_PBMC_01.raw	Raw
	Ctrl_PBMC_02.raw	Raw
	Ctrl_PBMC_03.raw	Raw
	HU_BI_24h_Hardjo_1.msf	Msf
	HU_BI_24h_Hardjo_1.pdResult	Other

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Multi-omics profiling of the host response to Leptospira infection in human PBMCs

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