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

J Infect Dis. 2021 Feb 13;223(3):517-521. 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.

Keywords: RNA expression; anti; cytokine storm; interleukin-10; soluble leishmania antigen; visceral leishmaniasis; whole-blood assays.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Protozoan / blood
  • Antibodies, Protozoan / genetics
  • Antibodies, Protozoan / immunology*
  • Antigens, Protozoan / blood
  • Antigens, Protozoan / immunology*
  • Cytokines / immunology
  • Gene Expression
  • Humans
  • Interferon-gamma / immunology
  • Interleukin-10 / immunology*
  • Leishmania donovani / immunology
  • Leishmaniasis, Visceral / immunology*
  • Tumor Necrosis Factor-alpha

Substances

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Cytokines
  • IL10 protein, human
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma