Article: article from journal or magazin.
An essential role for transmembrane TNF in the resolution of the inflammatory lesion induced by Leishmania major infection.
European Journal of Immunology
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.
Animals, Antibody Formation/immunology, Female, Immunoglobulin G/blood, Immunoglobulin G/immunology, Inflammation/immunology, Inflammation/parasitology, Interferon-gamma/metabolism, Leishmaniasis, Cutaneous/immunology, Leishmaniasis, Cutaneous/parasitology, Lymph Nodes/immunology, Lymph Nodes/metabolism, Membrane Proteins/genetics, Membrane Proteins/physiology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Knockout, Mice, Transgenic, Neutrophils/immunology, Neutrophils/parasitology, Nitric Oxide Synthase Type II/metabolism, Skin/metabolism, Skin/parasitology, Th1 Cells/immunology, Th1 Cells/metabolism, Tumor Necrosis Factor-alpha/genetics, Tumor Necrosis Factor-alpha/physiology
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