Host Inactivation of Bacterial Lipopolysaccharide Prevents Prolonged Tolerance Following Gram-Negative Bacterial Infection

Mingfang Lu, Alan W. Varley, Shoichiro Ohta, John Hardwick, Robert S. Munford

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

A transient state of tolerance to microbial molecules accompanies many infectious diseases. Such tolerance is thought to minimize inflammation-induced injury, but it may also alter host defenses. Here we report that recovery from the tolerant state induced by Gram-negative bacteria is greatly delayed in mice that lack acyloxyacyl hydrolase (AOAH), a lipase that partially deacylates the bacterial cell-wall lipopolysaccharide (LPS). Whereas wild-type mice regained normal responsiveness within 14 days after they received an intraperitoneal injection of LPS or Gram-negative bacteria, AOAH-deficient mice had greatly reduced proinflammatory responses to a second LPS injection for at least 3 weeks. In contrast, LPS-primed Aoah- knockout mice maintained an anti-inflammatory response, evident from their plasma levels of interleukin-10 (IL-10). LPS-primed Aoah-knockout mice experiencing prolonged tolerance were highly susceptible to virulent E. coli challenge. Inactivating LPS, an immunostimulatory microbial molecule, is thus important for restoring effective host defenses following Gram-negative bacterial infection in animals.

Original languageEnglish (US)
Pages (from-to)293-302
Number of pages10
JournalCell Host and Microbe
Volume4
Issue number3
DOIs
StatePublished - Sep 11 2008

Keywords

  • MICROBIO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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