A gene-expression program reflecting the innate immune response of cultured intestinal epithelial cells to infection by Listeria monocytogenes

Genome Biol. 2003;4(1):R2. doi: 10.1186/gb-2002-4-1-r2. Epub 2002 Dec 23.

Abstract

Background: Listeria monocytogenes is a Gram-positive, facultative, intracellular bacterial pathogen found in soil, which occasionally causes serious food-borne disease in humans. The outcome of an infection is dependent on the state of the infected individual's immune system, neutrophils being key players in clearing the microorganism from the body. The first line of host defense, however, is the intestinal epithelium.

Results: We have examined the transcriptional response of cultured human intestinal epithelial cells to infection by L. monocytogenes, which replicates in the host cell cytoplasm and spreads from cell to cell using a form of actin-based motility. We found that the predominant host response to infection was mediated by NFkappaB. To determine whether any host responses were due to recognition of specific virulence factors during infection, we also examined the transcriptional response to two bacterial mutants; actA which is defective in actin-based motility, and prfA, which is defective in the expression of all L. monocytogenes virulence genes. Remarkably, we found no detectable difference in the host transcriptional response to the wild-type and mutant bacteria.

Conclusions: These results suggest that cultured intestinal epithelial cells are capable of mounting and recruiting a powerful innate immune response to L. monocytogenes infection. Our results imply that L. monocytogenes is not specifically detected in the host cytoplasm of Caco-2 cells by intracellular signals. This suggests that entry of bacteria is mediated in the host cell post-translationally, and that these bacteria seek the cytosol not only for the nutrient-rich environment, but also for protection from detection by the immune system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Caco-2 Cells / metabolism*
  • Caco-2 Cells / microbiology
  • Chemokines / genetics
  • Chemokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Profiling*
  • Humans
  • Immunity, Innate / genetics
  • Listeria monocytogenes / genetics
  • Listeria monocytogenes / pathogenicity*
  • Membrane Proteins / genetics
  • Mutation
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Peptide Termination Factors
  • Signal Transduction
  • Time Factors
  • Trans-Activators / genetics
  • Virulence / genetics

Substances

  • Bacterial Proteins
  • Chemokines
  • Membrane Proteins
  • NF-kappa B
  • Peptide Termination Factors
  • Trans-Activators
  • actA protein, Listeria monocytogenes