Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, Gosselies, Belgium.
School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, 4072, Australia.
Sci Rep. 2017 Jul 21;7(1):6165. doi: 10.1038/s41598-017-06496-2.
Infection of C57Bl/6 mice by pleomorphic African trypanosomes Trypanosoma brucei and T. congolense is characterized by parasitemia waves coupled with the production of systemic levels of TNF. This cytokine is known to control T. brucei growth, but also to contribute to tissue damage, shortening the survival time of infected mice. Using a dominant-negative version of TNF to discriminate between the effects of the membrane-form versus the soluble form of TNF, we show that the second form is involved in neither parasite control nor induction of liver injury. Therefore, soluble TNF is likely not a major contributor to disease outcome. We propose that membrane-bound TNF is responsible for both T. brucei control and host pathology.
感染 C57Bl/6 小鼠的多形性非洲锥虫(布氏锥虫和刚果锥虫)的特征是寄生虫血症波伴随着全身水平的 TNF 产生。这种细胞因子已知可控制布氏锥虫的生长,但也会导致组织损伤,缩短感染小鼠的存活时间。使用 TNF 的显性负变体来区分 TNF 的膜形式和可溶性形式的作用,我们表明第二种形式既不参与寄生虫控制也不参与肝损伤的诱导。因此,可溶性 TNF 不太可能是疾病结果的主要贡献者。我们提出膜结合的 TNF 负责控制布氏锥虫和宿主病理。