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Absence of tumor necrosis factor supports alternative activation of macrophages in the liver after infection with Leishmania major

Citation

Hu, S and Marshall, C and Darby, J and Wei, W and Lyons, AB and Korner, H, Absence of tumor necrosis factor supports alternative activation of macrophages in the liver after infection with Leishmania major, Frontiers in Immunology, 9 Article 1. ISSN 1664-3224 (2018) [Refereed Article]


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Copyright 2018 The Authors Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.3389/fimmu.2018.00001

Abstract

The absence of tumor necrosis factor (TNF) causes lethal infection by Leishmania major in normally resistant C57BL/6J (B6.WT) mice. The underlying pathogenic mechanism of this fatal disease has so far remained elusive. We found that B6.WT mice deficient for the tnf gene (B6.TNF-/-) displayed not only a non-healing cutaneous lesion but also a serious infection of the liver upon L. major inoculation. Infected B6.TNF-/- mice developed an enlarged liver that showed increased inflammation. Furthermore, we detected an accumulating monocyte-derived macrophage population (CD45+F4/80+CD11bhiLy6Clow) that displayed a M2 macrophage phenotype with high expression of CD206, arginase-1, and IL-6, supporting the notion that IL-6 could be involved in M2 differentiation. In in vitro experiments, we demonstrated that IL-6 upregulated M-CSF receptor expression and skewed monocyte differentiation from dendritic cells to macrophages. This was countered by the addition of TNF. Furthermore, TNF interfered with the activation of IL-6-induced gp130-signal transducer and activator of transcription (STAT) 3 and IL-4-STAT6 signaling, thereby abrogating IL-6-facilitated M2 macrophage polarization. Therefore, our results support the notion of a general role of TNF in the inflammatory activation of macrophages and define a new role of IL-6 signaling in macrophage polarization downstream of TNF.

Item Details

Item Type:Refereed Article
Keywords:Leishmania major, liver, tumor necrosis factor, monocytes, il-6
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Immunology not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Infectious Diseases
Author:Hu, S (Miss Shanshan Hu)
Author:Marshall, C (Mr Cameron Marshall)
Author:Darby, J (Ms Jocelyn Darby)
Author:Lyons, AB (Dr Bruce Lyons)
Author:Korner, H (Professor Heinrich Korner)
ID Code:125079
Year Published:2018
Deposited By:Menzies Institute for Medical Research
Deposited On:2018-03-27
Last Modified:2018-04-12
Downloads:10 View Download Statistics

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