皮肤引流淋巴结萎缩使慢性肠道线虫感染的小鼠对二次感染的免疫反应受损。
Atrophy of skin-draining lymph nodes predisposes for impaired immune responses to secondary infection in mice with chronic intestinal nematode infection.
机构信息
Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China.
出版信息
PLoS Pathog. 2018 May 17;14(5):e1007008. doi: 10.1371/journal.ppat.1007008. eCollection 2018 May.
Intestinal nematodes suppress immune responses in the context of allergy, gut inflammation, secondary infection and vaccination. Several mechanisms have been proposed for this suppression including alterations in Th2 cell differentiation and increased Treg cell suppressive function. In this study, we show that chronic nematode infection leads to reduced peripheral responses to vaccination because of a generalized reduction in the available responsive lymphocyte pool. We found that superficial skin-draining lymph nodes (LNs) in mice that are chronically infected with the intestinal nematode Heligmosomides polygyrus, do not reach the same cellularity as worm-free mice upon subsequent BCG infection in the skin. B cells and T cells, all declined in skin-draining LN of H. polygyrus-infected mice, resulting in LNs atrophy and altered lymphocyte composition. Importantly, anti-helminthic treatment improved lymphocyte numbers in skin-draining LN, indicating that time after de-worming is critical to regain full-scale LN cellularity. De-worming, and time for the skin LN to recover cellularity, also mended responses to Bacille Calmette-Guerin (BCG) in the LN draining the footpad injection site. Thus, our findings show that chronic nematode infection leads to a paucity of lymphocytes in peripheral lymph nodes, which acts to reduce the efficacy of immune responses at these sites.
肠道线虫在过敏、肠道炎症、继发感染和疫苗接种的情况下抑制免疫反应。已经提出了几种这种抑制的机制,包括 Th2 细胞分化的改变和增加的 Treg 细胞抑制功能。在这项研究中,我们表明慢性线虫感染导致对外周疫苗接种的反应减少,因为可用的反应性淋巴细胞池普遍减少。我们发现,慢性感染肠道线虫 Heligmosomides polygyrus 的小鼠的浅层皮肤引流淋巴结 (LNs) 在皮肤中随后感染卡介苗 (BCG) 时,其细胞数量不会像无虫小鼠那样达到相同的水平。在 H. polygyrus 感染小鼠的皮肤引流 LN 中,B 细胞和 T 细胞均减少,导致淋巴结萎缩和淋巴细胞组成改变。重要的是,抗蠕虫治疗改善了皮肤引流 LN 中的淋巴细胞数量,表明驱虫后的时间对于恢复 LN 细胞数量至关重要。驱虫和皮肤 LN 恢复细胞数量的时间也修复了足部注射部位引流淋巴结对卡介苗 (BCG) 的反应。因此,我们的研究结果表明,慢性线虫感染导致外周淋巴结中淋巴细胞数量减少,从而降低这些部位免疫反应的效力。