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Free Content Patency of Litomosoides sigmodontis infection depends on Toll‐like receptor 4 whereas Toll‐like receptor 2 signalling influences filarial‐specific CD4+ T‐cell responses

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BALB/c mice develop a patent state [release of microfilariae (Mf), the transmission life‐stage, into the periphery] when exposed to the rodent filariae Litomosoides sigmodontis. Interestingly, only a portion of the infected mice become patent, which reflects the situation in human individuals infected with Wuchereria bancrofti. Since those individuals had differing filarial‐specific profiles, this study compared differences in immune responses between Mf+ and Mf infected BALB/c mice. We demonstrate that cultures of total spleen or mediastinal lymph node cells from Mf+ mice produce significantly more interleukin‐5 (IL‐5) to filarial antigens but equal levels of IL‐10 when compared with Mf mice. However, isolated CD4+ T cells from Mf+ mice produced significantly higher amounts of all measured cytokines, including IL‐10, when compared with CD4+ T‐cell responses from Mf mice. Since adaptive immune responses are influenced by triggering the innate immune system we further studied the immune profiles and parasitology in infected Toll‐like receptor‐2‐deficient (TLR2−/−) and TLR4−/− BALB/c mice. Ninety‐three per cent of L. sigmodontis‐exposed TLR4−/− BALB/c mice became patent (Mf+) although worm numbers remained comparable to those in Mf+ wild‐type controls. Lack of TLR2 had no influence on patency outcome or worm burden but infected Mf+ mice had significantly lower numbers of Foxp3+ regulatory T cells and dampened peripheral immune responses. Interestingly, in vitro culturing of CD4+ T cells from infected wild‐type mice with granulocyte–macrophage colony‐stimulating factor‐derived TLR2−/− dendritic cells resulted in an overall diminished cytokine profile to filarial antigens. Hence, triggering TLR4 or TLR2 during chronic filarial infection has a significant impact on patency and efficient CD4+ T‐cell responses, respectively.
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Keywords: Litomosoides sigmodontis; Toll‐like receptor 2; Toll‐like receptor 4; cytokines; immune regulation; microfilariae

Document Type: Research Article

Publication date: April 1, 2016

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