B cells are essential for vaccination-induced resistance to virulent Toxoplasma gondii
B cells are essential for vaccination-induced resistance to virulent Toxoplasma gondii
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DOI：
10.1128/iai.68.3.1026-1033.2000
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发表时间：
2000-03-01
影响因子：
3.1
通讯作者：
Johnson, LL
中科院分区：
文献类型：
--
作者：
Sayles, PC;Gibson, GW;Johnson, LL
已知T淋巴细胞和干扰素是弓形虫感染免疫抵抗的介质，但B细胞是否也发挥重要作用尚不清楚。我们已经用B细胞缺陷(Mu MT)小鼠研究了这个问题。如果接种了减毒的弓形虫速殖子，Mu MT小鼠很容易受到高毒力速殖子的攻击，而同样接种了B细胞充足的小鼠则能抵抗。挑战感染部位的寄生虫数量增加和广泛的死亡率证明了易感性。B细胞缺陷小鼠的易感性似乎不是由T细胞功能缺陷或接种和挑战B细胞缺陷小鼠产生干扰素-伽马的能力减弱引起的。给免疫B细胞缺陷小鼠注射弓形虫免疫血清，而不是非免疫血清，可显著延长它们在受到强毒速殖子攻击后的存活时间。缺乏Fe受体或补体第五组分的免疫小鼠抵抗攻击感染，这表明抗体包被的速殖子的Fc受体依赖的吞噬作用、抗体依赖的细胞毒性和抗体和补体依赖的裂解都不是速殖子抵抗的关键机制。然而，弓形虫免疫血清在体外能有效抑制速殖子对宿主细胞的感染。综上所述，这些结果支持这样的假设，即疫苗接种诱导对强毒速殖子的抵抗力需要B细胞来产生抗体，并且抗体可能通过阻断速殖子对宿主细胞的感染而在体内发挥保护性作用。
T lymphocytes and gamma interferon (IFN-gamma) are known mediators of immune resistance to Toxoplasma gondii infection, but whether B cells also play an important role is not clear. We have investigated this issue using B-cell-deficient (mu MT) mice. If vaccinated with attenuated T. gondii tachyzoites, mu MT mice are susceptible to a challenge intraperitoneal infection with highly virulent tachyzoites that similarly vaccinated B-cell-sufficient mice resist. Susceptibility is evidenced by increased numbers of parasites at the challenge infection site and by extensive mortality. The susceptibility of B-cell-deficient mice does not appear to be caused by deficient T-cell functions or diminished capacity of vaccinated and challenged B-cell-deficient mice to produce IFN-gamma. Administration of Toxoplasma-immune serum, but not nonimmune serum, to vaccinated B-cell-deficient mice significantly prolongs their survival after challenge with virulent tachyzoites. Vaccinated mice lacking Fe receptors or the fifth component of complement resist a challenge infection, suggesting that neither Fc-receptor-dependent phagocytosis of antibody-coated tachyzoites nor antibody-dependent cellular cytotoxicity nor antibody-and-complement-dependent lysis of tachyzoites is a crucial mechanism of resistance. However, Toxoplasma-immune serum effectively inhibits the infection of host cells by tachyzoites in vitro. Together, the results support the hypothesis that B cells are required for vaccination-induced resistance to virulent tachyzoites in order to produce antibodies and that antibodies may function protectively in vivo by blacking infection of host cells by tachyzoites.