The Role of B-cells and IgM Antibodies in Parasitemia, Anemia, and VSG Switching in Trypanosoma brucei–Infected Mice

Abstract

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 (µMT) 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 that the initial setting of peak levels of parasitemia in Trypanosoma brucei–infected µMT 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 µMT 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, whereas parasite-induced IgM antibodies played only a limited role in the outcome of the infection.

Role of Cytokines in <i>Trypanosoma brucei</i>-Induced Anaemia: A Review of the Literature

“…In trypanosomiasis, studies suggest that it may play a crucial role in the pathogenesis of anaemia, through modulation of cell growth and the phagocytosis of erythrocytes by macrophages 28 . Mice with TNF-α knockout have less severe anaemia and overall morbidity following trypanosomal infection 29 .…”

The Central Role of Macrophages in Trypanosomiasis-Associated Anemia:Rationale for Therapeutical Approaches

“…parasite growth) to polarization and the quality of subsequent adaptive (T-cell and B-cell mediated) immune responses. Indeed, upon infection with African trypanosomes, both arms of the hosts' immune system are activated comprising (i) a strong type I cellular immune response, consisting of pro-inflammatory molecules (TNF, IL-1, IL-6, NO) produced mainly by "classically" activated macrophages (M1) and (ii) a strong humoral anti-trypanosome B-cell response [18,19]. This response, induced during the early phase of infection, is sufficient to control parasite development and ensuring temporary host resistance.…”

Understanding the role of monocytic cells in liver inflammation using parasite infection as a model

“…Indeed, T. evansi causes the induction of IFN-g, TNF and NO as T. brucei or T. congolense. However, in contrast to T. brucei-and T. congolense-infection, none of these molecules is crucial for parasitemia control and survival of T. evansi-infected mice; only IgM antibodies contribute significantly to the control of the latter parasite (Barkhuizen et al 2007(Barkhuizen et al , 2008Magez et al 2008). Thus, the regulatory mechanisms underlying parasite control as well as the induction of immunopathogenicity may depend on specific host-parasite interactions.…”