Weidanz William P, Batchelder Joan M, Flaherty P, LaFleur G, Wong C, van der Heyde H C
Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706 1532, USA.
Exp Parasitol. 2005 Oct;111(2):97-104. doi: 10.1016/j.exppara.2005.06.006.
Our previous observation that B-cell-deficient JH-/- mice utilize T cell-dependent immunity to suppress acute Plasmodium chabaudi adami-induced malaria but then develop chronic low-level parasitemia prompted this study of control mechanisms for chronic parasitemia. When we infected JH-/- mice with blood-stage parasites, chronic parasitemia exacerbated after the 6th month and persisted for up to 17 months. This exacerbation of parasitemia could not be attributed to host aging because the time-course of acute infection in naïve aged mice was nearly identical to that seen in young mice. Nor could exacerbated parasitemia be attributed to mutation in the parasite genome resulting in increased virulence; when subinoculated into naïve JH-/- mice, parasites from chronically infected JH-/- mice with exacerbated parasitemia produced acute stage parasitemia profiles in most recipients comparable to those seen in JH-/- mice upon infection with the original stabilate material. Of the pro-inflammatory cytokines measured, including IFNgamma, TNFalpha, IL-12p70, and MCP-1beta, none were significantly different in the sera of mice with exacerbated parasitemia compared to uninfected controls. Levels of IL-6 were significantly (P=0.002) less in the sera of mice with exacerbated parasitemia. Serum levels of the anti-inflammatory cytokine, TGFbeta, were significantly depressed in chronically infected JH-/- mice compared to uninfected controls. In contrast, IL-10 levels were markedly increased. These findings suggest that the cytokine balance may be disturbed during chronic malaria, thereby impacting on mechanisms that modulate levels of parasitemia.
我们之前观察到，B细胞缺陷的JH-/-小鼠利用T细胞依赖性免疫来抑制急性查巴迪疟原虫诱导的疟疾，但随后会发展为慢性低水平寄生虫血症，这促使我们对慢性寄生虫血症的控制机制进行研究。当我们用血液期寄生虫感染JH-/-小鼠时，慢性寄生虫血症在第6个月后加剧，并持续长达17个月。这种寄生虫血症的加剧不能归因于宿主衰老，因为未感染的老龄小鼠急性感染的时间进程与年轻小鼠几乎相同。寄生虫血症加剧也不能归因于寄生虫基因组的突变导致毒力增加；当将来自慢性感染且寄生虫血症加剧的JH-/-小鼠的寄生虫接种到未感染的JH-/-小鼠中时，大多数接受者产生的急性期寄生虫血症情况与用原始稳定株材料感染JH-/-小鼠时所见的情况相当。在所检测的促炎细胞因子中，包括IFNγ、TNFα、IL-12p70和MCP-1β，与未感染的对照相比，寄生虫血症加剧的小鼠血清中这些细胞因子均无显著差异。寄生虫血症加剧的小鼠血清中IL-6水平显著降低（P = 0.002）。与未感染的对照相比，慢性感染的JH-/-小鼠血清中抗炎细胞因子TGFβ的水平显著降低。相反，IL-10水平明显升高。这些发现表明，慢性疟疾期间细胞因子平衡可能受到干扰，从而影响调节寄生虫血症水平的机制。
