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

• Published in: The Journal of infectious diseases Vol. 223; no. 3; pp. 517 - 521
• Main Authors: Singh, Om Prakash, Syn, Genevieve, Nylén, Susanne, Engwerda, Christian, Sacks, David, Wilson, Mary E, Kumar, Rajiv, Chakravarty, Jaya, Sundar, Shyam, Blackwell, Jenefer M, Fakiola, Michaela
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 13.02.2021
• Subjects: Antigens; Chemokines; Cytokine storm; Cytokines; IL-1β; Interleukin 1; Interleukin 10; Interleukin 6; Major and Brief Reports; Medicin och hälsovetenskap; Parasitic diseases; Soluble leishmanial antigen; Transcription; Tumor necrosis factor; Tumor necrosis factor-TNF; Visceral leishmaniasis; γ-Interferon; RNA expression; cytokine storm; soluble leishmania antigen; visceral leishmaniasis; interleukin-10; whole-blood assays; anti
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiaa381

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.