TRIM21 controls Toll-like receptor 2 responses in bone-marrow-derived macrophages

TRIM21 is an interferon-stimulated E3 ligase that controls the activity of pattern-recognition signaling via ubiquitination of interferon regulatory factors and DDX41. Previous studies on the role of TRIM21 in innate immune responses have yielded contradictory results, suggesting that the role of TRIM21 is cell specific. Here, we report that bone-marrow-derived macrophages (BMDMs) generated from Trim21^-/- mice have reduced expression of mature macrophage markers. Reflecting their reduced differentiation in response to macrophage colony-stimulating factor (M-CSF), Trim21^-/- BMDMs had decreased expression of M-CSF signature genes. Although Trim21^-/- BMDMs responded normally to Toll-like receptor 9 (TLR9) activation, they produced lower levels of pro-inflammatory cytokines in response to the TLR2 agonist PAM3CSK4. In line with this, the response to infection with the Bacillus Calmette-Guérin strain of Mycobacterium bovis was also diminished in Trim21^-/- BMDMs. Our results indicate that TRIM21 controls responses to TLR2 agonists.