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

doi:10.1016/j.chom.2020.04.012

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

Aberdeen Centre For Environmental Sustainability

City University of New York
German Cancer Research Center
Dartmouth College

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

11 Downloads (Pure)

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 language	English
Pages (from-to)	79-88.e4
Number of pages	9
Journal	Cell Host & Microbe
Volume	28
Issue number	1
Early online date	15 May 2020
DOIs	https://doi.org/10.1016/j.chom.2020.04.012
Publication status	Published - 8 Jul 2020

Bibliographical note

Acknowledgments
This work was supported by NSF Bread award IOS-1249166 and Hunter College (J.R.); CUNY Science Scholarship (J.V.); Hunter College HHMI UGRAD Science Education grant 52007535 (E.H.); NIH/NIAID award AI085973 (N.P.); Wellcome Trust award 082786 (J.S.). We thank George Cross and Ana Rodriguez for the parasite lines and VSG preparations used in this study.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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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© 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Accepted author manuscript, 3.1 MBLicence: CC BY-NC-ND

Cite this

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title = "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.",

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author = "Joseph Verdi and Ronnie Zipkin and Elani Hillman and Gertsch, \{Rahel A.\} and Pangburn, \{Sarah J.\} and Russell Thomson and Nina Papavasiliou and Jeremy Sternberg and Jayne Raper",

note = "Acknowledgments This work was supported by NSF Bread award IOS-1249166 and Hunter College (J.R.); CUNY Science Scholarship (J.V.); Hunter College HHMI UGRAD Science Education grant 52007535 (E.H.); NIH/NIAID award AI085973 (N.P.); Wellcome Trust award 082786 (J.S.). We thank George Cross and Ana Rodriguez for the parasite lines and VSG preparations used in this study.",

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doi = "10.1016/j.chom.2020.04.012",

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AU - Verdi, Joseph

AU - Zipkin, Ronnie

AU - Hillman, Elani

AU - Gertsch, Rahel A.

AU - Pangburn, Sarah J.

AU - Thomson, Russell

AU - Papavasiliou, Nina

AU - Sternberg, Jeremy

AU - Raper, Jayne

N1 - Acknowledgments This work was supported by NSF Bread award IOS-1249166 and Hunter College (J.R.); CUNY Science Scholarship (J.V.); Hunter College HHMI UGRAD Science Education grant 52007535 (E.H.); NIH/NIAID award AI085973 (N.P.); Wellcome Trust award 082786 (J.S.). We thank George Cross and Ana Rodriguez for the parasite lines and VSG preparations used in this study.

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N2 - 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.

AB - 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.

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KW - apolipoprotein L-1

KW - innate immunity

KW - AFRICAN TRYPANOSOMES

KW - VARIANT SURFACE GLYCOPROTEINS

KW - PROTEIN

KW - NORMAL HUMAN-SERUM

KW - CELL-SURFACE

KW - BRUCEI

KW - HAPTOGLOBIN

KW - DISTINCT ROLES

KW - TRYPANOLYTIC FACTOR

KW - APOL1

UR - https://www.scopus.com/pages/publications/85085286455

U2 - 10.1016/j.chom.2020.04.012

DO - 10.1016/j.chom.2020.04.012

M3 - Article

C2 - 32416060

SN - 1931-3128

VL - 28

SP - 79-88.e4

JO - Cell Host & Microbe

JF - Cell Host & Microbe

IS - 1

ER -

Inducible Germline IgMs Bridge Trypanosome Lytic Factor Assembly and Parasite Recognition

Abstract

Bibliographical note

UN SDGs

Keywords

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