Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital of Bonn, Sigmund Freud Str. 25, 53127, Bonn, Germany.
LIMES, University of Bonn, Bonn, Germany.
Parasitol Res. 2019 Feb;118(2):539-549. doi: 10.1007/s00436-018-6159-1. Epub 2019 Jan 15.
Worldwide approximately 68 million people are infected with lymphatic filariasis (Lf), provoked by Wuchereria bancrofti, Brugia malayi and Brugia timori. This disease can lead to massive swelling of the limbs (elephantiasis) and disfigurement of the male genitalia (hydrocele). Filarial induced immune regulation is characterised by dominant type 2 helper T cell and regulatory immune responses. In vitro studies have provided evidence that signalling via Toll-like receptor-mediated pathways is triggered by filarial associated factors. Nevertheless, until now, less is known about the role of the adapter molecule TRIF during in vivo infections. Here, we used the rodent-specific nematode Litomosoides sigmodontis to investigate the role of TLR signalling and the corresponding downstream adapter and regulatory molecules TRIF, MyD88, IRF1 and IRF3 during an ongoing infection in semi-susceptible C57BL/6 mice. Interestingly, lack of the central adapter molecule TRIF led to higher worm burden and reduced overall absolute cell numbers in the thoracic cavity (the site of infection) 30 days post-infection. In addition, frequencies of macrophages and lymphocytes in the TC were increased in infected TRIF C57BL/6 mice, whereas frequencies of eosinophils, CD4 and CD8 T cells were reduced. Nevertheless, cytokine levels and regulatory T cell populations remained comparable between TRIF-deficient and wildtype C57BL/6 mice upon 30 days of L. sigmodontis infection. In summary, this study revealed a crucial role of the adapter molecule TRIF on worm recovery and immune cell recruitment into the site of infection 30 days upon L. sigmodontis infection in C57BL/6 mice.
全球约有 6800 万人感染淋巴丝虫病（Lf），由班氏吴策线虫、马来丝虫和帝汶丝虫引起。这种疾病可导致四肢严重肿胀（象皮病）和男性生殖器畸形（鞘膜积液）。丝虫诱导的免疫调节以主导型 2 辅助 T 细胞和调节性免疫反应为特征。体外研究已经提供了证据，表明丝虫相关因子通过 Toll 样受体介导的途径触发信号转导。然而，到目前为止，人们对衔接分子 TRIF 在体内感染中的作用知之甚少。在这里，我们使用特定于啮齿动物的线虫利什曼原虫来研究 TLR 信号及其相应的下游衔接和调节分子 TRIF、MyD88、IRF1 和 IRF3 在半易感 C57BL/6 小鼠持续感染过程中的作用。有趣的是，中央衔接分子 TRIF 的缺失导致感染后 30 天胸腔（感染部位）中的蠕虫负荷增加和总绝对细胞数减少。此外，感染 TRIF C57BL/6 小鼠的 TC 中的巨噬细胞和淋巴细胞的频率增加，而嗜酸性粒细胞、CD4 和 CD8 T 细胞的频率降低。然而，在感染利什曼原虫 30 天后，TRIF 缺陷型和野生型 C57BL/6 小鼠之间的细胞因子水平和调节性 T 细胞群仍然相当。总之，这项研究揭示了衔接分子 TRIF 在 C57BL/6 小鼠感染利什曼原虫后 30 天内对蠕虫恢复和免疫细胞募集到感染部位的重要作用。
