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

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. 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 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 , 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 induces intrinsic apoptosis of 5T33MM cells , 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.