Ing R, Su Z, Scott M E, Koski K G
Institute of Parasitology and School of Dietetics and Human Nutrition, McGill University (Macdonald Campus), 21,111 Lakeshore Road, Ste-Anne de Bellevue, Quebec H9X 3V9, Canada.
Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7078-83. doi: 10.1073/pnas.97.13.7078.
Protein malnutrition may increase susceptibility to gastrointestinal parasitic infections, possibly as a result of impaired intestinal and/or systemic T helper 2 (Th2) effector responses induced by down-regulation of Th2 cytokines and/or up-regulation of Th1 cytokines. To test this hypothesis, female BALB/c mice (n = 18/diet) were fed a control (24%), marginal (7%), or deficient (3%) protein diet and given a challenge infection with Heligmosomoides polygyrus. The 3% mice had higher worm burdens at 1, 2, and 4 weeks postchallenge infection (pci), lower increases in serum IgE, reduced intestinal eosinophilia, and depressed mucosal mast cell proliferation and activation at 1-2 weeks pci. To determine whether these suppressed effector responses resulted from altered spleen and mesenteric lymph node (MLN) cytokine production, cells were restimulated in vitro with parasite antigen and cytokine concentrations were measured. Deficient MLN cells secreted significantly less IL-4 and more IFN-gamma at 1-2 weeks pci than did control MLN cells. Deficient spleen cells also secreted more IFN-gamma at 2 weeks pci compared with control spleen cells. From reverse transcription-PCR analyses, the 3% mice also had lower IL-4 mRNA level in spleen and MLN at 1-2 weeks pci. Our study supports the hypothesis that protein malnutrition increases the survival of a nematode parasite by decreasing gut-associated IL-4 (Th2) and increasing IFN-gamma (Th1) within 2 weeks pci, leading to reduced intestinal and systemic Th2 effector responses.
蛋白质营养不良可能会增加对胃肠道寄生虫感染的易感性，这可能是由于Th2细胞因子下调和/或Th1细胞因子上调所诱导的肠道和/或全身辅助性T细胞2（Th2）效应反应受损所致。为了验证这一假设，将雌性BALB/c小鼠（每组18只）分别喂食对照（24%）、边缘（7%）或缺乏（3%）蛋白质的饮食，并给予多房棘球绦虫感染挑战。3%蛋白质组的小鼠在感染后1周、2周和4周时虫负荷更高，血清IgE升高幅度更低，肠道嗜酸性粒细胞减少，且在感染后1 - 2周时黏膜肥大细胞增殖和活化受到抑制。为了确定这些受抑制的效应反应是否源于脾脏和肠系膜淋巴结（MLN）细胞因子产生的改变，用寄生虫抗原在体外对细胞进行再刺激并测量细胞因子浓度。在感染后1 - 2周时，缺乏蛋白质组的MLN细胞分泌的IL - 4显著少于对照MLN细胞，而分泌的IFN - γ更多。与对照脾脏细胞相比，缺乏蛋白质组的脾脏细胞在感染后2周时也分泌更多的IFN - γ。从逆转录 - PCR分析来看，3%蛋白质组的小鼠在感染后1 - 2周时脾脏和MLN中的IL - 4 mRNA水平也更低。我们的研究支持以下假设：蛋白质营养不良通过在感染后2周内降低肠道相关的IL - 4（Th2）并增加IFN - γ（Th1），从而增加线虫寄生虫的存活率，导致肠道和全身Th2效应反应减弱。
