Infection of BALB/c mice with microfilariae (mf) of Brugia pahangi leads to the suppression of antigen (Ag)-specific proliferative responses in the spleen. The proliferative defect is dependent on inducible nitric oxide synthase (iNOS) activity, since inhibition of iNOS with either l-N-monomethyl arginine (l-NMMA) or aminoguanidine reversed defective proliferation. Splenocytes from mf-infected animals produce high levels of gamma interferon (IFN-γ) upon in vitro restimulation with Ag, and experiments in IFN-γ receptor-deficient (IFN-γR?/?) mice demonstrated that signaling via the IFN-γR is essential in the induction of NO production and subsequent proliferative suppression. Restimulation of splenocytes from mf-infected animals with an extract of Acanthocheilonema viteae, a related filarial worm which lacks endosymbiotic bacteria, also resulted in NO production and proliferative suppression, demonstrating that lipopolysaccharide of bacterial origin is not essential to the induction of iNOS activity. These results extend previous observations that infection with different life cycle stages of Brugia leads to the development of differentially polarized immune responses and demonstrate one method by which these differences may exert their effects on the proliferative potential of cells from infected animals.
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机译：用Bemcia pahangi 的微丝aria（mf）感染BALB / c小鼠可抑制脾脏中抗原（Ag）特异性增殖反应。增殖缺陷取决于诱导型一氧化氮合酶（iNOS）活性，因为用1- N -单甲基精氨酸（1-NMMA）或氨基胍抑制iNOS可逆转缺陷增殖。用Ag体外再刺激后，来自mf感染动物的脾细胞产生高水平的γ-干扰素（IFN-γ），并证明了在IFN-γ受体缺陷型（IFN-γR？/？）小鼠中的实验IFN-γR的信号传导在诱导NO产生和随后的增殖抑制中至关重要。用缺乏内共生细菌的相关丝虫棘皮动物线虫提取物重新刺激mf感染动物的脾细胞，也导致NO的产生和增殖抑制，这表明细菌来源的脂多糖不是必需的诱导iNOS活性。这些结果扩展了以前的观察结果，即以不同的生命周期阶段的 Brugia 感染会导致差异极化的免疫反应的发展，并证明了这些差异可能通过一种方法对感染细胞的增殖潜能产生影响。动物。
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