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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Trypanosomiasis-induced B cell apoptosis results in loss of protective anti-parasite antibody responses and abolishment of vaccine-induced memory responses
PLoS Pathogens, Volume 4, No. 5, Article e1000078, Year 2008
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Description
African trypanosomes of the Trypanosoma brucei species are extra-cellular parasites that cause human African trypanosomiasis (HAT) as well as infections in game animals and livestock. Trypanosomes are known to evade the immune response of their mammalian host by continuous antigenic variation of their surface coat. Here, we aim to demonstrate that in addition, trypanosomes (i) cause the loss of various B cell populations, (ii) disable the hosts' capacity to raise a long-lasting specific protective anti-parasite antibody response, and (iii) abrogate vaccine-induced protective response to a non-related human pathogen such as Bordetella pertussis. Using a mouse model for T. brucei, various B cell populations were analyzed by FACS at different time points of infection. The results show that during early onset of a T. brucei infection, spleen remodeling results in the rapid loss of the IgM+ marginal zone (IgM+MZ) B cell population characterized as B220+IgM HighIgDInt CD21HighCD23LowCD1d +CD138-. These cells, when isolated during the first peak of infection, stained positive for Annexin V and had increased caspase-3 enzyme activity. Elevated caspase-3 mRNA levels coincided with decreased mRNA levels of the anti-apoptotic Bcl-2 protein and BAFF receptor (BAFF-R), indicating the onset of apoptosis. Moreover, affected B cells became unresponsive to stimulation by BCR cross-linking with anti-IgM Fab fragments. In vivo, infection-induced loss of IgM+ B cells coincided with the disappearance of protective variant-specific Tindependent IgM responses, rendering the host rapidly susceptible to re-challenge with previously encountered parasites. Finally, using the well-established human diphtheria, tetanus, and B. pertussis (DTPa) vaccination model in mice, we show that T. brucei infections abrogate vaccine-induced protective responses to a non-related pathogen such as B. pertussis. Infections with T. brucei parasites result in the rapid loss of T-cell independent IgM+MZ B cells that are normally functioning as the primary immune barrier against blood-borne pathogens. In addition, ongoing trypanosome infections results in the rapid loss of B cell responsiveness and prevent the induction of protective memory responses. Finally, trypanosome infections disable the host's capacity to recall vaccine-induced memory responses against non-related pathogens. In particular, these last results call for detailed studies of the effect of HAT on memory recall responses in humans, prior to the planning of any mass vaccination campaign in HAT endemic areas. © 2008 Radwanska et al.
Authors & Co-Authors
Radwanska, Magdalena
Belgium, Brussels
Université Libre de Bruxelles
de Trez, Carl
Belgium, Brussels
Université Libre de Bruxelles
Ryffel, Bernhard
France, Paris
Cnrs Centre National de la Recherche Scientifique
Black, Samuel J.
United States, Amherst
University of Massachusetts Amherst
Magez, Stefan
Belgium, Brussels
Vrije Universiteit Brussel
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Statistics
Citations: 124
Authors: 5
Affiliations: 5
Identifiers
Doi:
10.1371/journal.ppat.1000078
ISSN:
15537374
Research Areas
Cancer
Study Design
Cross Sectional Study