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.

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.

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