Oncotarget

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This article has been corrected. Correction in: Oncotarget. 2018; 9:22871.

Experimental African trypanosome infection suppresses the development of multiple myeloma in mice by inducing intrinsic apoptosis of malignant plasma cells

Nathan De Beule, Eline Menu _, Mathieu J.M. Bertrand, Mérédis Favreau, Elke De Bruyne, Ken Maes, Kim De Veirman, Magdalena Radwanska, Afshin Samali, Stefan Magez, Karin Vanderkerken and Carl De Trez

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Oncotarget. 2017; 8:52016-52025. https://doi.org/10.18632/oncotarget.18152

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Abstract

Nathan De Beule1,*, Eline Menu1,*, Mathieu J.M. Bertrand2,3, Mérédis Favreau1,4, Elke De Bruyne1, Ken Maes1, Kim De Veirman1, Magdalena Radwanska4, Afshin Samali 5,6, Stefan Magez7,8, Karin Vanderkerken1 and Carl De Trez8

1 Department of Hematology and Immunology-Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium

2 Inflammation Research Center, VIB, Zwijnaarde-Ghent, Belgium

3 Department of Biomedical Molecular Biology, Ghent University, Zwijnaarde-Ghent, Belgium

4 Department of Molecular Immunology and Inflammation, VIB Inflammation Research Center, Ghent University, Ghent, Belgium

5 Apoptosis Research Centre, NUI Galway, Ireland

6 School of Natural Sciences, NUI Galway, Ireland

7 Ghent University Global Campus, Yeonsu-Gu, Incheon, South Korea

8 Department of Structural Biology Research Center (SBRC), Research Unit of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Flanders Institute for Biotechnology (VIB), Brussels, Belgium

* These authors have contributed equally to the work

Correspondence to:

Eline Menu, email:

Keywords: multiple myeloma, T. brucei

Received: March 02, 2017 Accepted: May 04, 2017 Published: May 24, 2017

Abstract

Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells in the bone marrow (BM). Recently, several studies have highlighted the role of pathogens in either promoting or dampening malignancies of unrelated origin. Trypanosoma brucei is an extracellular protozoan parasite which causes sleeping sickness. Our group has previously demonstrated that trypanosome infection affects effector plasma B cells. Therefore, we hypothesized that T. brucei infection could have an impact on MM development. Using the immunocompetent 5T33MM model, we demonstrated a significant reduction in BM-plasmacytosis and M-protein levels in mice infected with T. brucei, resulting in an increased survival of these mice. Blocking IFNγ could only partially abrogate these effects, suggesting that other mechanisms are involved in the destruction of malignant plasma cells. We found that T. brucei induces intrinsic apoptosis of 5T33MM cells in vivo, and that this was associated with reduced endogenous unfolded protein response (UPR) activation. Interestingly, pharmacological inhibition of IRE1α and PERK was sufficient to induce apoptosis in these cells. Together, these results demonstrate that trypanosome infections can interfere with MM development by suppressing endogenous UPR activation and promoting intrinsic apoptosis.


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