Type III IFNs Are Commonly Induced by Bacteria-Sensing TLRs and Reinforce Epithelial Barriers during Infection

J Immunol. 2017 Nov 1;199(9):3270-3279. doi: 10.4049/jimmunol.1700250. Epub 2017 Sep 27.


Type III IFNs (IFN-λs) are secreted factors that are well-known for their antiviral activities. However, their regulation and functions during bacterial infections are unclear. In this article, we report that the regulation of IFN-λ genes did not track with mechanisms that control type I IFN expression in response to TLRs. Whereas type I IFNs were only expressed from TLRs present on endosomes, type III IFNs could be induced by TLRs that reside at the plasma membrane and that detect various bacterial products. The mechanisms that regulate type III IFN gene expression tracked with those that promote inflammatory cytokine and chemokine expression. Importantly, rIFN-λs enhanced epithelial barriers in vitro, preventing transcellular bacteria dissemination. We therefore propose that in addition to their functions in cell-intrinsic antiviral immunity, type III IFNs protect epithelial barrier integrity, an activity that would benefit the host during any infectious encounter.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacteria / immunology*
  • Bacterial Infections / genetics
  • Bacterial Infections / immunology*
  • Bacterial Infections / pathology
  • Cell Line, Tumor
  • Epithelium / immunology
  • Epithelium / pathology
  • Gene Expression Regulation / immunology*
  • Humans
  • Interferons / genetics
  • Interferons / immunology*
  • Mice
  • Mice, Knockout
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / immunology*


  • Toll-Like Receptors
  • Interferons