MBM-Mesenchymal Stem Cells as a vehicle for immunization of mice against Bordetella pertussis

Abstract

Abstract Mesenchymal Stem Cells (MSC) derived from bone marrow is well documented to lack immunogenic features and demonstrate anti-inflammatory characteristics. Additionally, in vitro treatment of MSCs with IFNγ was previously shown to increase expression of antigen-presenting molecules such as MHC class II. Therefore in this study, we hypothesize that MSC can serve as an immunization vehicle to deliver Bordetella pertussis (Bp) antigens. MSC were isolated from bone marrow. To confirm MSC characteristics, cells were differentiated into chondrocytes, adipocytes and osteocytes. Flow cytometry and immunofluorescence were used to demonstrate that the propagated MSCs express high level of MHC II when pretreated with IFNγ. IFNγ treated MSC were then pulsed overnight with heat-killed B. pertussis and intranasally administered (one million/mouse) twice with one-week interval. Mice were then challenged with Bp infection. Mice immunized with MSC/Bp were 100% protected from the infection challenge as measured by the bacterial load in lungs at 5dpi. Th17 are required for effective resolution of B. pertussis infection, but those immune responses are mounted only late p.i. In contrast, mice immunized with INFγ+/MSC/Bp, display a high frequency of Th17 cells in the lungs that was detected as early as 5dpi. These preliminary data suggest that BM-MSCs can serve as a vector to protect mice from Bp infection. We will further investigate for the precise immune responses induced by MSC/Bp vaccine.