Both TLR2 and TRIF contribute to interferon-β production during Listeria infection

Camille Aubry (1, 2) , Sinead C. Corr (3) , Sebastian Wienerroither (4) , Céline Goulard (2) , Ruth Jones (3) , Amanda M. Jamieson (4) , Thomas Decker (4) , Luke A. J. O'Neill (3) , Olivier Dussurget (1, 2) , Pascale Cossart (2)

1 UPD7 - Université Paris Diderot - Paris 7
2 UIBC - Interactions Bactéries-Cellules
3 Trinity College Dublin
4 University of Vienna [Vienna]

Synthesis of interferon-beta (IFN-beta) is an innate response to cytoplasmic infection with bacterial pathogens. Our recent studies showed that Listeria monocytogenes limits immune detection and IFN-beta synthesis via deacetylation of its peptidoglycan, which renders the bacterium resistant to lysozyme degradation. Here, we examined signaling requirements for the massive IFN-beta production resulting from the infection of murine macrophages with a mutant strain of L. monocytogenes, Delta pgdA, which is unable to modify its peptidoglycan. We report the identification of unconventional signaling pathways to the IFN-beta gene, requiring TLR2 and bacterial internalization. Induction of IFN-beta was independent of the Mal/TIRAP adaptor protein but required TRIF and the transcription factors IRF3 and IRF7. These pathways were stimulated to a lesser degree by wild-type L. monocytogenes. They operated in both resident and inflammatory macrophages derived from the peritoneal cavity, but not in bone marrow-derived macrophages. The novelty of our findings thus lies in the first description of TLR2 and TRIF as two critical components leading to the induction of the IFN-beta gene and in uncovering that individual macrophage populations adopt different strategies to link pathogen recognition signals to IFN-beta gene expression.

Domaines: Sciences du Vivant [q-bio]

Camille Aubry, Sinead C. Corr, Sebastian Wienerroither, Céline Goulard, Ruth Jones, et al.. Both TLR2 and TRIF contribute to interferon-β production during Listeria infection. PLoS ONE, 2012, 7 (3), pp.285-290. ⟨10.1371/journal.pone.0033299⟩. ⟨hal-02650491⟩