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

Om Prakash Singh; Genevieve Syn; Susanne Nylén; Christian Engwerda; David Sacks; Mary E. Wilson; Rajiv Kumar; Jaya Chakravarty; Shyam Sundar; Jenefer M. Blackwell; Michaela Fakiola

doi:10.1093/infdis/jiaa381

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

Om Prakash Singh, Genevieve Syn, Susanne Nylén, Christian Engwerda, David Sacks, Mary E. Wilson, Rajiv Kumar, Jaya Chakravarty, Shyam Sundar, Jenefer M. Blackwell, Michaela Fakiola

UWA Centre for Child Health Research (affiliated with the The Kids Research Institute Australia)

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

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.

Original language	English
Pages (from-to)	517-521
Number of pages	5
Journal	The Journal of infectious diseases
Volume	223
Issue number	3
DOIs	https://doi.org/10.1093/infdis/jiaa381
Publication status	Published - 1 Feb 2021

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10.1093/infdis/jiaa381

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881328/

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title = "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.",

keywords = "anti, cytokine storm, interleukin-10, RNA expression, soluble leishmania antigen, visceral leishmaniasis, whole-blood assays",

author = "Singh, {Om Prakash} and Genevieve Syn and Susanne Nyl{\'e}n and Christian Engwerda and David Sacks and Wilson, {Mary E.} and Rajiv Kumar and Jaya Chakravarty and Shyam Sundar and Blackwell, {Jenefer M.} and Michaela Fakiola",

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T1 - Anti-Interleukin-10 Unleashes Transcriptional Response to Leishmanial Antigens in Visceral Leishmaniasis Patients

AU - Singh, Om Prakash

AU - Syn, Genevieve

AU - Nylén, Susanne

AU - Engwerda, Christian

AU - Sacks, David

AU - Wilson, Mary E.

AU - Kumar, Rajiv

AU - Chakravarty, Jaya

AU - Sundar, Shyam

AU - Blackwell, Jenefer M.

AU - Fakiola, Michaela

PY - 2021/2/1

Y1 - 2021/2/1

N2 - 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.

AB - 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.

KW - anti

KW - cytokine storm

KW - interleukin-10

KW - RNA expression

KW - soluble leishmania antigen

KW - visceral leishmaniasis

KW - whole-blood assays

UR - http://www.scopus.com/inward/record.url?scp=85097388839&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiaa381

DO - 10.1093/infdis/jiaa381

M3 - Article

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AN - SCOPUS:85097388839

SN - 0022-1899

VL - 223

SP - 517

EP - 521

JO - The Journal of infectious diseases

JF - The Journal of infectious diseases

IS - 3

ER -

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

Abstract

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