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.
Highlights
An increasing number of publications have confirmed the positive or in rare cases the negative relationship existing between infectious agents and cancer
It is striking to note that T. brucei infection of MM mice, 7 days post-5T33MM administration significantly reduced bone marrow (BM) plasmacytosis by 35% compared to uninfected 5T33MM mice twenty days after MM inoculation
To date no information has been published on the evolution of parasitemia and survival of C57BL/KaLwRij mice infected with T. brucei
Summary
An increasing number of publications have confirmed the positive or in rare cases the negative relationship existing between infectious agents and cancer. Many bacteria or viruses were shown to exert a malignancy enhancing role. In 2012, a study published in Lancet attributed 16% of cancer occurring in 2008 to bacteria or viruses [1]. In Africa, this rate more than doubled as 36% of all cancers potentially result from infection [2]. Haematological malignancies, such as multiple myeloma (MM), have become a major www.impactjournals.com/oncotarget cause of death and disability in developing countries and in Sub-Saharan Africa, where it should start to slowly eclipse pathogenic diseases, such as HIV and malaria by 2030 [3]. Due to the accumulation of malignant plasma cells, typical MM related end-organ damage can occur, such as anemia, renal failure, osteolytic lesions and immunosuppression [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
