Related Experiment Video
Updated: Dec 18, 2025

A Macrophage Reporter Cell Assay to Examine Toll-Like Receptor-Mediated NF-kB/AP-1 Signaling on Adsorbed Protein Layers on Polymeric Surfaces
Published on: January 7, 2020
Cutting Edge: TNF Is Essential for Mycobacteria-Induced MINCLE Expression, Macrophage Activation, and Th17
Judith Schick1, Johanna Schäfer1, Christian Alexander2
1Institut für Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
Abstract:
TNF blockade is a successful treatment for human autoimmune disorders like rheumatoid arthritis and inflammatory bowel disease yet increases susceptibility to tuberculosis and other infections. The C-type lectin receptors (CLR) MINCLE, MCL, and DECTIN-2 are expressed on myeloid cells and sense mycobacterial cell wall glycolipids. In this study, we show that TNF is sufficient to upregulate MINCLE, MCL, and DECTIN-2 in macrophages. TNF signaling through TNFR1 p55 was required for upregulation of these CLR and for cytokine secretion in macrophages stimulated with the MINCLE ligand trehalose-6,6-dibehenate or infected with Mycobacterium bovis bacillus Calmette-Guérin. The Th17 response to immunization with the MINCLE-dependent adjuvant trehalose-6,6-dibehenate was specifically abrogated in TNF-deficient mice and strongly attenuated by TNF blockade with etanercept. Together, interference with production or signaling of TNF antagonized the expression of DECTIN-2 family CLR, thwarting vaccine responses and possibly increasing infection risk.
Insights
Tumor necrosis factor (TNF) blockade upregulates C-type lectin receptors (CLRs) like MINCLE, MCL, and DECTIN-2 in macrophages, impacting immune responses and vaccine efficacy.
Area of Science:
- Immunology
- Molecular Biology
- Microbiology
Background:
- Tumor necrosis factor (TNF) blockade is effective for autoimmune diseases but increases infection susceptibility.
- C-type lectin receptors (CLRs), including MINCLE, MCL, and DECTIN-2, are crucial for sensing microbial components on myeloid cells.
Purpose of the Study:
- To investigate the role of TNF in regulating CLR expression on macrophages.
- To determine the impact of TNF on immune responses to mycobacterial antigens and vaccine adjuvants.
Main Methods:
- Macrophage cultures treated with TNF and/or MINCLE ligands.
- Stimulation with *Mycobacterium bovis* bacillus Calmette-Guérin (BCG).
- Analysis of CLR expression and cytokine secretion.
- Assessment of Th17 responses in TNF-deficient mice and mice treated with etanercept (TNF blockade).
Main Results:
- TNF administration upregulated MINCLE, MCL, and DECTIN-2 expression in macrophages.
- TNF signaling via TNFR1 p55 was essential for CLR upregulation and cytokine secretion.
- TNF blockade or deficiency abrogated Th17 responses to a MINCLE-dependent adjuvant.
Conclusions:
- TNF signaling is critical for the expression of DECTIN-2 family CLRs.
- Interference with TNF antagonizes CLR expression, potentially impairing vaccine responses and increasing infection risk.
More Related Videos
07:42Fluorescence Assays for the Study of Mycobacterium tuberculosis Interaction with the Immune Receptor SLAMF1
Published on: February 28, 2025
11:48Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes
Published on: May 31, 2018
Related Concept Videos
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
Defense Against Bacterial Pathogens
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...