Doligalska M, Donskow-Schmelter K, Rzepecka J, Drela N
Department of Parasitology, University of Warsaw, Warsaw, Poland.
Parasite Immunol. 2007 Jun;29(6):283-91. doi: 10.1111/j.1365-3024.2007.00946.x.
We evaluated levels of apoptosis and the immune response ex vivo in BALB/c mice infected with Heligmosomoides polygyrus. Cell proliferation, apoptosis and cytokine production were measured in mesenteric lymph nodes (MLN) without exposure to H. polygyrus antigens in culture. The inhibited apoptosis and cytokine production reported might reflect a state of cell hyporesponsiveness in the prepatent phase of infection. These changes were accompanied by changes in the percentage of CD4+ cells in MLN and popliteal lymph nodes (PLN). The prolonged reduction in apoptosis coexisted with induced cell proliferation, elevated TNF-alpha, IL-12p70, IFN-gamma, IL-6, IL-10 and TGF-beta synthesis, but lowered IL-4 and IL-2 levels. In the chronic phase of infection an increasing production of IFN-gamma, monocyte chemotactic protein-1 (MCP-1), IL-10 and TGF-beta with decreasing concentrations of other cytokines resulted in restored apoptosis. The cytokine response in serum showed moderate production of TNF-alpha, temporary involvement of IL-12p70, induction of IFN-gamma and IL-10 synthesis, as well as growing IL-6 and MCP-1 production. It is suggested that a synchronized synthesis of distinct cytokines is accompanied by different levels of inhibited apoptosis during the prepatent and chronic phases of H. polygyrus infection in BALB/c mice. We suggest that immunosuppression provoked by the nematode is not the outcome of parasite-induced apoptosis, but rather results from a hyporesponsiveness experienced by cells during H. polygyrus infection.
我们评估了感染多枝单睾线虫的BALB/c小鼠体内的凋亡水平和体外免疫反应。在不接触培养物中多枝单睾线虫抗原的情况下,检测肠系膜淋巴结(MLN)中的细胞增殖、凋亡和细胞因子产生情况。所报道的凋亡抑制和细胞因子产生可能反映了感染潜伏期细胞低反应状态。这些变化伴随着MLN和腘窝淋巴结(PLN)中CD4+细胞百分比的改变。凋亡的长期减少与诱导的细胞增殖、TNF-α、IL-12p70、IFN-γ、IL-6、IL-10和TGF-β合成升高同时存在,但IL-4和IL-2水平降低。在感染慢性期,IFN-γ、单核细胞趋化蛋白-1(MCP-1)、IL-10和TGF-β产生增加,其他细胞因子浓度降低,导致凋亡恢复。血清中的细胞因子反应显示TNF-α产生适度,IL-12p70短暂参与,IFN-γ和IL-10合成诱导,以及IL-6和MCP-1产生增加。提示在BALB/c小鼠多枝单睾线虫感染的潜伏期和慢性期,不同细胞因子的同步合成伴随着不同程度的凋亡抑制。我们认为线虫引发的免疫抑制不是寄生虫诱导凋亡的结果,而是多枝单睾线虫感染期间细胞低反应的结果。