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Anti-Interleukin-10 Unleashes Transcriptional Response to Leishmanial Antigens in Visceral Leishmaniasis Patients.

ABSTRACT: Visceral leishmaniasis (VL; Leishmania donovani) cases produce interferon-γ and tumor necrosis factor in response to soluble leishmanial antigen (SLA) in whole-blood assays. Using transcriptional profiling, we demonstrate the impact of interleukin-10 (IL-10), a cytokine implicated in VL, on this response. SLA stimulation identified 28 differentially expressed genes (DEGs), 17/28 in a single network with TNF as hub. SLA plus anti-IL-10 produced 454 DEGs, 292 in a single network with TNF, IFNG, NFKBIA, IL6, and IL1B as hubs in concert with a remarkable chemokine/cytokine storm. Our data demonstrate the singular effect of IL-10 as a potent immune modulator in VL.

SUBMITTER: Singh OP

PROVIDER: S-EPMC7881328 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Anti-Interleukin-10 Unleashes Transcriptional Response to Leishmanial Antigens in Visceral Leishmaniasis Patients.

Singh Om Prakash OP Syn Genevieve G Nylén Susanne S Engwerda Christian C Sacks David D Wilson Mary E ME Kumar Rajiv R Chakravarty Jaya J Sundar Shyam S Blackwell Jenefer M JM Fakiola Michaela M

The Journal of infectious diseases 20210201 3

Visceral leishmaniasis (VL; Leishmania donovani) cases produce interferon-γ and tumor necrosis factor in response to soluble leishmanial antigen (SLA) in whole-blood assays. Using transcriptional profiling, we demonstrate the impact of interleukin-10 (IL-10), a cytokine implicated in VL, on this response. SLA stimulation identified 28 differentially expressed genes (DEGs), 17/28 in a single network with TNF as hub. SLA plus anti-IL-10 produced 454 DEGs, 292 in a single network with TNF, IFNG, NF ...[more]

PMID: 32614452

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Anti-Interleukin-10 unleashes transcriptional response to leishmanial antigen in whole blood of visceral leishmaniasis patients

Project description:Visceral leishmaniasis (VL; Leishmania donovani) cases produce interferon- (IFN) and tumour necrosis factor (TNF) in response to soluble leishmanial antigen (SLA) in whole blood assays. These pro-inflammatory cytokines are crucial for activation of macrophages to kill L. donovani parasites. Detailed immunological studies comparing active with cured patients suggest that a balance exists between the pro-inflammatory cytokines TNF and IFN, and anti-inflammatory interleukin-10 (IL10). Our interest was to obtain a global understanding of the response to SLA in whole blood from active VL cases, and to determine what effect neutralising anti-IL10 would have on this response. Transcriptional profiles following SLA stimulation of whole blood from VL patients showed very few differentially expressed genes (DEGs), the majority belonging to a single network with TNF at the hub. In contrast, when anti-IL10 was added with SLA, hundreds of DEGs were observed, 65% belonging to a single network with TNF, IFNG, NFKBIA, IL6 and IL1B as hub genes in concert with a remarkable chemokine/cytokine storm. Our data demonstrate the singular impact of IL10 as a potent immune modulator in VL.

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Anti-Interleukin-10 unleashes transcriptional response to leishmanial antigen in whole blood of visceral leishmaniasis patients

Project description:Anti-Interleukin-10 unleashes transcriptional response to leishmanial antigen in whole blood of visceral leishmaniasis patients

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