An essential role for transmembrane TNF in the resolution of the inflammatory lesion induced by Leishmania major infection
An essential role for transmembrane TNF in the resolution of the inflammatory lesion induced by Leishmania major infection
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DOI：
10.1002/eji.200737662
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发表时间：
2008-03-01
影响因子：
5.4
通讯作者：
Tacchini-Cottier, Fabienne
中科院分区：
文献类型：
--
作者：
Allenbach, Cindy;Launois, Pascal;Tacchini-Cottier, Fabienne
TNF是主要利什曼原虫感染的重要参与者，有助于控制炎症病变，并在较小程度上杀死寄生虫。然而，在这些过程中的可溶性和跨膜形式的TNF的相对贡献是未知的。探讨跨膜型肿瘤坏死因子（mTNF）在L.主要感染，mTNF-敲入（mTNF（Delta/Delta））小鼠，其表达功能性mTNF但不释放可溶性TNF，用L. major，并将炎性病变和免疫应答的发展与L.主要感染的TNF-/-和野生型小鼠。mTNF（Delta/Delta）小鼠控制感染，并与野生型小鼠一样解决其炎症病变，这一过程与寄生虫感染部位的中性粒细胞早期清除有关。与此相反，L.主要感染的TNF-/-小鼠出现了不愈合的损伤，其特征在于在感染部位中性粒细胞的存在升高，并且损伤内寄生虫数量得到部分控制。总之，本文提供的结果表明，在不存在可溶性TNF的情况下，mTNF足以控制由L.主要，能够调节炎症，并在感染部位最佳杀死利什曼原虫。
TNF is an essential player in infections with Leishmania major, contributing to the control of the inflammatory lesion and, to a lesser degree, to parasite killing. However, the relative contribution of the soluble and transmembrane forms of TNF in these processes is unknown. To investigate the role of transmembrane TNF (mTNF) in the control of L. major infections, mTNF-knock-in (mTNF(Delta/Delta)) mice, which express functional mTNF but do not release soluble TNF, were infected with L. major, and the development of the inflammatory lesion and the immune response was compared to that occurring in L. major-infected TNF-/- and wild-type mice. mTNF(Delta/Delta) mice controlled the infection and resolved their inflammatory lesion as well as wild-type mice, a process associated with the early clearance of neutrophils at the site of parasite infection. In contrast, L. major-infected TNF-/- mice developed non-healing lesions, characterized by an elevated presence of neutrophils at the site of infection and partial control of parasite number within the lesions. Altogether, the results presented here demonstrate that mTNF, in absence of soluble TNF, is sufficient to control infection due to L. major, enabling the regulation of inflammation, and the optimal killing of Leishmania parasites at the site of infection.