Inducible Germline IgMs Bridge Trypanosome Lytic Factor Assembly and Parasite Recognition

Joseph Verdi, Ronnie Zipkin, Elani Hillman, Rahel A. Gertsch, Sarah J. Pangburn, Russell Thomson, Nina Papavasiliou, Jeremy Sternberg, Jayne Raper* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Trypanosomiasis is a devastating neglected tropical disease affecting livestock and humans. Humans are susceptible to two Trypanosoma brucei subspecies but protected from other trypanosomes by circulating high-density lipoprotein (HDL) complexes called trypanosome lytic factors (TLFs) 1 and 2. TLFs contain apolipoprotein L-1 contributing to lysis and haptoglobin-related protein (HPR), which can function as a ligand for a parasite receptor. TLF2 also uniquely contains non-covalently associated immunoglobin M (IgM) antibodies, the role and origin of which remain unclear. Here, we show that these TLF2-associated IgMs interact with both HPR and alternate trypanosome surface proteins, including variant surface glycoprotein, likely facilitating complex biogenesis and TLF uptake into parasites. TLF2-IgMs are germline antibodies that, while present at basal concentrations in healthy individuals, are elicited by trypanosome infection in both murine models and human sleeping sickness patients. These data suggest that poly- and self-reactive germline antibodies such as TLF2-associated IgMs play a role in antimicrobial immunity.
Original languageEnglish
Pages (from-to)79-88.e4
Number of pages9
JournalCell Host & Microbe
Volume28
Issue number1
Early online date15 May 2020
DOIs
Publication statusPublished - 8 Jul 2020

Keywords

  • trypanosome lytic factors
  • variant surface glycoprotein
  • haptoglobin-related protein
  • natural germline antibodies
  • immunoglobulin M
  • IgM
  • apolipoprotein L-1
  • innate immunity
  • AFRICAN TRYPANOSOMES
  • VARIANT SURFACE GLYCOPROTEINS
  • PROTEIN
  • NORMAL HUMAN-SERUM
  • CELL-SURFACE
  • BRUCEI
  • HAPTOGLOBIN
  • DISTINCT ROLES
  • TRYPANOLYTIC FACTOR
  • APOL1

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  • Cite this

    Verdi, J., Zipkin, R., Hillman, E., Gertsch, R. A., Pangburn, S. J., Thomson, R., Papavasiliou, N., Sternberg, J., & Raper, J. (2020). Inducible Germline IgMs Bridge Trypanosome Lytic Factor Assembly and Parasite Recognition. Cell Host & Microbe, 28(1), 79-88.e4. https://doi.org/10.1016/j.chom.2020.04.012