The role of B-cells and IgM antibodies in parasitemia, anemia, and VSG switching in Trypanosoma brucei-infected mice
The role of B-cells and IgM antibodies in parasitemia, anemia, and VSG switching in Trypanosoma brucei-infected mice
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DOI：
10.1371/journal.ppat.1000122
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发表时间：
2008-08-01
期刊：
影响因子：
6.7
通讯作者：
Brombacher, Frank
中科院分区：
文献类型：
--
作者：
Magez, Stefan;Schwegmann, Anita;Brombacher, Frank
非洲锥虫是细胞外寄生原生动物，主要通过噬血采采蝇的叮咬传播。被认为介导哺乳动物宿主寄生虫病控制的主要机制是抗体与寄生虫表面（由变异特异性表面糖蛋白覆盖）之间的持续相互作用。早期的实验研究表明，b细胞反应具有很强的保护作用，但受到vsg特异性的限制。我们使用b细胞（mu MT）和IgM缺陷（IgM(-/-)）小鼠来研究b细胞和IgM抗体在寄生虫病控制和体内诱导锥虫病相关贫血中的作用。这些感染研究表明，在感染布鲁氏锥虫的mu MT和IgM（-/-）小鼠中，寄生虫血症峰值的初始设置与b细胞的存在无关。然而，b细胞有助于周期性地降低循环寄生虫水平，并且是长期生存所必需的，而IgM抗体在这一过程中仅发挥有限的作用。在mu MT小鼠和IgM（-/-）小鼠感染期间，感染相关贫血被假设为由b细胞反应介导，并且独立于感染诱导的宿主抗体反应发生。抗原变异是非洲锥虫的主要免疫逃避机制，它独立于宿主对寄生虫不断变化的抗原糖蛋白外壳的抗体反应。总之，这些结果表明，在小鼠实验布鲁氏锥虫病中，b细胞对周期性峰值寄生虫血症清除至关重要，而寄生虫诱导的IgM抗体在感染结果中仅发挥有限的作用。
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 (mu MT) 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 mu MT 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 mu MT 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.