T cell suppression in the bone marrow of visceral leishmaniasis patients: impact of parasite load

Clin Exp Immunol. 2018 Mar;191(3):318-327. doi: 10.1111/cei.13074. Epub 2017 Nov 20.

Abstract

Visceral leishmaniasis (VL) is a disseminated and lethal disease of reticulo-endothelial system caused by protozoan parasites Leishmania donovani and L. infantum, which are known to induce host T cell suppression. To understand the impact of parasite load on T cell function, the present was focused on parasite load with T cell function in bone marrow of 26 VL patients. We observed significant enrichment of forkhead box protein 3 (FoxP3)+ (P = 0·0003) and interleukin (IL)-10+ FoxP3+ regulatory T cells (Treg ) (P = 0·004) in the bone marrow (BM) of patients with high parasite load (HPL) compared with low parasite load (LPL). Concordantly, T effector cells producing interferon (IFN)-γ (P = 0·005) and IL-17A (P = 0·002) were reduced in the BM of HPL. Blocking of Treg -cell derived suppressive cytokines [(IL-10 and transforming growth factor (TGF)-β] rescued the effector T cells and their functions. However, it was observed that TGF-β levels were dominant, favouring Treg cell differentiation. Furthermore, the low ratio of IL-6/TGF-β favours the suppressive milieu in HPL patients. Here we show the change in levels of various cytokines with the parasitic load during active VL, which could be helpful in devising newer immunotherapeutic strategies against this disease.

Keywords: Leishmania donovani; T regulatory cells (Treg); bone marrow aspirate (BMA); visceral leishmaniasis (VL).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Blocking / pharmacology
  • Bone Marrow / pathology*
  • Cells, Cultured
  • Child
  • Cytokines / metabolism
  • Female
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immunosuppression Therapy
  • Leishmania donovani / physiology*
  • Leishmaniasis, Visceral / immunology*
  • Leishmaniasis, Visceral / parasitology
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Parasite Load
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Young Adult

Substances

  • Antibodies, Blocking
  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors