Lipocalin-2 Resistance Confers an Advantage to Salmonella enterica Serotype Typhimurium for Growth and Survival in the Inflamed Intestine

Manuela Raffatellu, Michael D. George, Yuko Akiyama, Michael J. Hornsby, Sean Paul Nuccio, Tatiane A. Paixao, Brian P. Butler, Hiutung Chu, Renato L. Santos, Thorsten Berger, Tak W. Mak, Renee M Tsolis, Charles L Bevins, Jay V Solnick, Satya Dandekar, Andreas J Baumler

Research output: Contribution to journalArticle

309 Scopus citations

Abstract

In response to enteric pathogens, the inflamed intestine produces antimicrobial proteins, a process mediated by the cytokines IL-17 and IL-22. Salmonella enterica serotype Typhimurium thrives in the inflamed intestinal environment, suggesting that the pathogen is resistant to antimicrobials it encounters in the intestinal lumen. However, the identity of these antimicrobials and corresponding bacterial resistance mechanisms remain unknown. Here, we report that enteric infection of rhesus macaques and mice with S. Typhimurium resulted in marked Il-17- and IL-22-dependent intestinal epithelial induction and luminal accumulation of lipocalin-2, an antimicrobial protein that prevents bacterial iron acquisition. Resistance to lipocalin-2, mediated by the iroBCDE iroN locus, conferred a competitive advantage to the bacterium in colonizing the inflamed intestine of wild-type but not of lipocalin-2-deficient mice. Thus, resistance to lipocalin-2 defines a specific adaptation of S. Typhimurium for growth in the inflamed intestine.

Original languageEnglish (US)
Pages (from-to)476-486
Number of pages11
JournalCell Host and Microbe
Volume5
Issue number5
DOIs
StatePublished - May 8 2009

    Fingerprint

Keywords

  • MICROBIO

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this