Global Experts Meeting on Infectious Diseases
Ghent University Global Campus, South Korea
Title: Trypanosomiasis-induced B cell apoptosis results in loss of protective anti-parasite antibody responses and abolishment of vaccine-induced memory responses
Biography: Radwanska Magdalena
African trypanosomes maintain chronic infections by various evasion strategies. While antigenic variation of their Variant Specific Glycoprotein (VSG) surface coat is the most studied strategy linked to evading the host humoral response, African trypanosomes also induce impaired B-cell lymphopoiesis, destruction of the B-cell compartment and abrogation of memory responses.
At the level of both the immature transitional B-cell compartment and the marginal zone B-cells, infection-induced B-cell cell death in part is due to direct cell-cell contact as it can be inhibited by anti-tryponsome surface nanobodies or by physically separating trypanosomes from B-cells in a trans-well co-culture system. Here, induction of Capsase 3 activation is directly linked to the death of these cells during the onset of the first peak of infection. Infection associated apoptosis of follicular B cells correlates in turn to enhanced Fas death receptor surface expression and depends on the cucial role of IFN-γ in the early onset of cell destruction. Indeed, mice deficient for the cytokine or the receptor are protected from early-stage trypanosomosis-associated FoB cell depletion. Finally, also a role for NK cells and the granule pore-forming protein perforin has been shown, indicating that trypanosomes use a multitude of mechanisms to fight the host B-cell compartment. Together these mechanisms result in the ablation of the hosts’ capacity to mount an efficient antibody mediated defense, and prevent the buildup of immunological memory against parasite components. This successfully allows the parasite to re-use previously expressed VSG sequences throughout the infection without the risk of elimination by antibody-mediated destruction.