Epithelium-intrinsic NAIP/NLRC4 inflammasome drives infected enterocyte expulsion to restrict Salmonella replication in the intestinal mucosa

Cell Host Microbe. 2014 Aug 13;16(2):237-248. doi: 10.1016/j.chom.2014.07.001.


The gut mucosal epithelium separates the host from the microbiota, but enteropathogens such as Salmonella Typhimurium (S.Tm) can invade and breach this barrier. Defenses against such acute insults remain incompletely understood. Using a murine model of Salmonella enterocolitis, we analyzed mechanisms limiting pathogen loads in the epithelium during early infection. Although the epithelium-invading S.Tm replicate initially, this intraepithelial replicative niche is restricted by expulsion of infected enterocytes into the lumen. This mechanism is compromised if inflammasome components (NAIP1-6, NLRC4, caspase-1/-11) are deleted, or ablated specifically in the epithelium, resulting in ∼100-fold higher intraepithelial loads and accelerated lymph node colonization. Interestingly, the cytokines downstream of inflammasome activation, interleukin (IL)-1α/β and IL-18, appear dispensable for epithelial restriction of early infection. These data establish the role of an epithelium-intrinsic inflammasome, which drives expulsion of infected cells to restrict the pathogen's intraepithelial proliferation. This may represent a general defense mechanism against mucosal infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / physiology*
  • Calcium-Binding Proteins / physiology*
  • Cecum / microbiology
  • Cecum / pathology
  • Enterocytes / immunology
  • Enterocytes / microbiology*
  • Host-Pathogen Interactions
  • Inflammasomes
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuronal Apoptosis-Inhibitory Protein / physiology*
  • Salmonella Infections / immunology*
  • Salmonella typhimurium / immunology*


  • Apoptosis Regulatory Proteins
  • Calcium-Binding Proteins
  • Inflammasomes
  • Ipaf protein, mouse
  • Naip1 protein, mouse
  • Neuronal Apoptosis-Inhibitory Protein