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Inducible Germline IgMs Bridge Trypanosome Lytic Factor Assembly and Parasite Recognition.

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.

journal_name

Cell Host Microbe

journal_title

Cell host & microbe

authors

Verdi J,Zipkin R,Hillman E,Gertsch RA,Pangburn SJ,Thomson R,Papavasiliou N,Sternberg J,Raper J

doi

10.1016/j.chom.2020.04.012

subject

Has Abstract

pub_date

2020-07-08 00:00:00

pages

79-88.e4

issue

1

eissn

1931-3128

issn

1934-6069

pii

S1931-3128(20)30239-0

journal_volume

28

pub_type

杂志文章

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