期刊
ACTA TROPICA
卷 119, 期 2-3, 页码 144-150出版社
ELSEVIER
DOI: 10.1016/j.actatropica.2011.05.005
关键词
B cells; Toll-like receptors (TLRs); Malaria; Signal transduction
资金
- Swedish Agency for Research Development
- Swedish Research Council (VR)
- EviMalaR Network of Excellence
- BioMalPar European Network of Excellence [LSMP-CT-2004-503578]
- Priority 1 Life Sciences, Genomics and Biotechnology for Health in the 6th Framework Programme
Chronic malaria severely affects the immune system and causes polyclonal B-cell activation, as evidenced by the presence of hypergammaglobulinemia, elevated levels of autoantibodies, loss of B-cell memory and the frequent occurrence of Burkitt's lymphomas (BL) in children living in malaria endemic areas. Previous studies have shown that the cysteine-rich interdomain region 1 alpha (CIDR1 alpha) of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) of the FCR3S1.2 strain, subsequently named CIDR1a, interacts with B cells partially through the binding to the B-cell receptor (BCR). This interaction leads to an activated phenotype, increased survival, and a low degree of proliferation. CIDR1 alpha preferentially activates the memory B-cell compartment, therefore PfEMP1 is considered to act as a polyclonal B-cell activator and its role in memory maintenance has been suggested. In this report, we extend the analysis of the PfEMP1-CIDR1 alpha B-cell interaction and demonstrate that PfEMP1-CIDR1 alpha increases the expression of TLR7 and TLR10 mRNA transcripts and sensitizes B cells to TLR9 signalling via the MyD88 adaptor molecule. Furthermore, despite its ability to bind to surface Igs, PfEMP1-CIDR1 alpha-induced B-cell activation does not seem to proceed through the BCR, since it does not induce Lyn and/or phospho-tyrosine mediated signalling pathways. Rather PfEMP1-CIDR1 alpha induces the phosphorylation of downstream kinases, such as ERK1/2, p38 and IKB alpha, in human B cells. These findings indicate that PfEMP1-CIDR1 alpha induces a persistent activation of B cells, which in turn can contribute to the exhaustion and impairment of B-cell functions during chronic malaria infection. (C) 2011 Elsevier B.V. All rights reserved.
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