Leishmania donovani molecules recognized by sera of filaria infected host facilitate filarial infection

Parasitol Res. 2018 Sep;117(9):2901-2912. doi: 10.1007/s00436-018-5981-9. Epub 2018 Jun 26.

Abstract

We earlier found that F6 fraction of human filaria Brugia malayi cross-reacted with sera of Leishmania donovani infected hamsters and immunization with F6 inhibited both filarial and leishmanial infections. In the present study, we identified a 52.9-93.6 kDa fraction (Ld1) of L. donovani that cross-reacted with sera of B. malayi infected animals and investigated effect of Ld1 on filarial infection. Immunization of BALB/c mice with Ld1 facilitated B. malayi infection with remarkable increase in parasite burden. Facilitation of filarial infection was associated with downregulated cell proliferation, IL-5, IL-13, IFN-γ, TNF-α, and IL-2 levels and upregulated IL-4 and TGF-β. Ld1 exposure also suppressed MHC class-I, MHC class-II, and FcεR1 expression, and phagocytosis in naive mouse macrophages, and CD4+, CD8+, and CD19+ cell population in mouse spleen. Two-dimensional electrophoresis and matrix-assisted laser desorption ionization-time of flight-mass spectrometry revealed eight proteins in Ld1: putative heat shock protein (HSP) 70-related protein 1, HSP70 mitochondrial precursor, alanine aminotransferase, 2,3-bisphosphoglycerate-independent phosphoglycerate mutase, protein disulfide isomerase, putative ATPase beta subunit, trypanothione reductase, and a hypothetical protein. HSP70 protein mitochondrial precursor and trypanothione reductase showed homology with Trypanosoma cruzi and L. donovani, respectively, and the rest 6 proteins including hypothetical protein bear homology with L. infantum. In conclusion, the present study for the first time shows that immunization with filarial cross-reactive Ld1 fraction of L. donovani facilitates filarial infection by modulating Th1 and Th2 responses. Ld1 molecules may therefore facilitate filarial infection in filaria-leishmania co-infection.

Keywords: Brugia malayi; Cross-reactive molecules; IgG subclasses; Leishmania donovani; MALDI-TOF-MS; Th1 and Th2 cytokines.

MeSH terms

  • Animals
  • Brugia malayi / immunology*
  • Cell Proliferation
  • Coinfection / immunology
  • Coinfection / parasitology
  • Cricetinae
  • Cross Reactions / immunology*
  • Filariasis / immunology*
  • Filariasis / parasitology
  • Humans
  • Leishmania donovani / immunology*
  • Leishmaniasis / immunology*
  • Leishmaniasis / parasitology
  • Leishmaniasis, Visceral / immunology*
  • Leishmaniasis, Visceral / parasitology
  • Mice
  • Mice, Inbred BALB C
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Vaccination