Detrimental Effect of Trypanosoma brucei brucei Infection on Memory B Cells and Host Ability to Recall Protective B-cell Responses

Using 2 independent vaccination strategies, this study showed that trypanosomosis induces general immunological B-cell memory loss, which benefits the parasite by reducing the stringency for surface antigenic variation. Background Trypanosoma brucei brucei evades host immune responses by multiple means, including the disruption of B-cell homeostasis. This hampers anti-trypanosome vaccine development. Because the cellular mechanism underlying this pathology has never been addressed, our study focuses on the fate of memory B cells (MBCs) in vaccinated mice upon trypanosome challenge. Methods A trypanosome variant surface glycoprotein (VSG) and fluorescent phycoerythrin were used as immunization antigens. Functional and cellular characteristics of antigen-specific MBCs were studied after homologous and heterologous parasite challenge. Results Immunization with AnTat1.1 VSG triggers a specific antibody response and isotype-switched CD73(+)CD273(+)CD80(+) MBCs, delivering 90% sterile protection against a homologous parasite challenge. As expected, AnTat1.1 VSG immunization does not protect against infection with heterologous VSG-switched parasites. After successful curative drug treatment, mice were shown to have completely lost their previously induced protective immunity against the homologous parasites, coinciding with the loss of vaccine-induced MBCs. A phycoerythrin immunization approach confirmed that trypanosome infections cause the general loss of antigen-specific splenic and bone marrow MBCs and a reduction in antigen-specific immunoglobulin G. Conclusions Trypanosomosis induces general immunological memory loss. This benefits the parasites by reducing the stringency for antigenic variation requirements.

Automated summary

This study demonstrates that trypanosomosis induces general immunological B-cell memory loss, benefiting the parasite by reducing the requirements for surface antigenic variation.