The role of B-cells and IgM antibodies in parasitemia, anemia, and VSG switching in Trypanosoma brucei-infected mice

African trypanosomes are extracellular parasitic protozoa, predominantly transmitted by the bite of the haematophagic tsetse fly. The main mechanism considered to mediate parasitemia control in a mammalian host is the continuous interaction between antibodies and the parasite surface, covered by variant-specific surface glycoproteins. Early experimental studies have shown that B-cell responses can be strongly protective but are limited by their VSG-specificity.We have used B-cell (uMT) and IgM-deficient (IgM-/-) mice to investigate the role of B-cells and IGM antibodies in parasitemia control and the in vivo induction of trypanosomiasis-associated anemia. These infection studies revealed that the initial setting of peak levels of parasitemia in Trypanosoma brucei-infected uMT and IgM-/- mice occurred independent of the presence of B-cells. However, B-cells helped to periodically reduce circulating parasites levels and were required for long term survival, while IgM antibodies played only a limited role in this process. Infection-associated anemia, hypothesized to be mediated by B-cell responses, was induced during infection in uMT mice as well as in IgM-/- mice, and as such occurred independently from the infection-induced host antibody response. Antigenic variation, the main immune evasion mechanism of African trypanosomes, occurred independently from host antibody responses against the parasite's ever-changing antigenic glycoprotein coat. Collectively, these results demonstrated that in murine experimental T.brucei trypanosomiasis, B-cells were crucial for periodic peak parasitemia clearance, wheres parasite-induced IgM antibodies played only a limited role in the outcome of the infection.

Jaar van publicatie:2008

Trefwoorden:Trypanosoma brucei, B-cells, IgM antibodies, anemia, variant-specific surface glycoproteins