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

PLoS Pathogens

Anita Schwegmann¹  Frank Brombacher²  Stefan Magez²  Filip Claes²  Michael Drennan²  Robert Atkinson³  Patrick De Baetselier⁴ 

[1] Department of Molecular and Cellular Recognition, VIB, Brussels, Belgium;Division of Immunology, Institute for Infectious Diseases and Molecular Medicine (IIDMM), Health Science Faculty, University of Cape Town, and International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town, South Africa;Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Brussels, Belgium;Laboratory of Serology, Institute for Tropical Medicine “Prins Leopold”, Antwerpen, Belgium

关键词: Parasitic diseases;    Trypanosoma;    Antibodies;    B cells;    Parasitemia;    Anemia;    Trypanosomiasis;    Trypanosoma brucei gambiense;   

DOI  :  10.1371/journal.ppat.1000122

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY