The circulating immunoglobulins negatively impact on the parasite clearance in the liver of Leishmania donovani-infected mice via dampening ROS activity

Biochem Biophys Res Commun. 2018 Nov 17;506(1):20-26. doi: 10.1016/j.bbrc.2018.10.055. Epub 2018 Oct 15.

Abstract

Visceral leishmaniasis, the most severe form of leishmaniasis, is caused by Leishmania donovani and L. infantum. Immunity to Leishmania infection has been shown to depend on the development of Th1 cells; however, the roles of B cells and antibodies during infection remain unclear. In the present study, we showed that AID and μs double-deficient mice (DKO), which have B cells but not circulating immunoglobulins (cIgs), became resistant to L. donovani infection, whereas μs or AID single-deficient mice did not. This resistance in DKO mice occurred in the liver from an early stage of the infection. The depletion of IFN-γ did not affect the rapid reduction of parasite burden, whereas NADPH oxidases was up-regulated in the livers of infected DKO mice. The inhibition of the reactive oxygen species pathway in vivo by apocynin, a NADPH oxidase inhibitor, resulted in a significant increase in the parasite burden in DKO mice. These results indicate that a circulating Ig deficiency induces a protective response against L. donovani infection by elevating IFN-γ-independent NADPH oxidase activity, and also that cIgs play a regulatory role in controlling L. donovani infection in mice.

Keywords: AID and μs double-deficient mice; Circulating immunoglobulins; Interferon-γ; Leishmania donovani; NADPH oxidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / parasitology
  • Cytidine Deaminase / deficiency
  • Cytidine Deaminase / genetics*
  • Cytidine Deaminase / immunology
  • Disease Resistance / genetics*
  • Enzyme Activation
  • Female
  • Gene Expression Regulation
  • Genes, Reporter
  • Immune Sera / administration & dosage
  • Immunization, Passive / methods
  • Immunoglobulin mu-Chains / blood
  • Immunoglobulin mu-Chains / genetics*
  • Immunoglobulin mu-Chains / immunology
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Leishmania donovani / immunology*
  • Leishmania donovani / pathogenicity
  • Leishmaniasis, Visceral / genetics
  • Leishmaniasis, Visceral / immunology*
  • Leishmaniasis, Visceral / parasitology
  • Luciferases / genetics
  • Luciferases / metabolism
  • Mice
  • Mice, Knockout
  • NADPH Oxidases / genetics
  • NADPH Oxidases / immunology
  • Parasite Load
  • Reactive Oxygen Species / immunology*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Th1 Cells / immunology
  • Th1 Cells / parasitology

Substances

  • IFNG protein, mouse
  • Immune Sera
  • Immunoglobulin mu-Chains
  • Reactive Oxygen Species
  • Interferon-gamma
  • Luciferases
  • NADPH Oxidases
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase