An essential role for transmembrane TNF in the resolution of the inflammatory lesion induced by Leishmania major infection

被引:40
作者
Allenbach, Cindy [1 ]
Launois, Pascal [1 ]
Mueller, Christoph [2 ]
Tacchini-Cottier, Fabienne [1 ]
机构
[1] Univ Lausanne, WHO Immunol Res & Training Ctr, Dept Biochem, CH-1066 Epalinges, Switzerland
[2] Univ Bern, Dept Pathol, CH-3000 Bern, Switzerland
关键词
inflammation; Leishmania major; neutrophils; transmembrane TNF;
D O I
10.1002/eji.200737662
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:720 / 731
页数:12
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