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

46 Citations (Scopus)

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

Fingerprint

Gram-Negative Bacterial Infections
Lipopolysaccharides
Gram-Negative Bacteria
Knockout Mice
Intraperitoneal Injections
Lipase
Interleukin-10
Cell Wall
Communicable Diseases
Anti-Inflammatory Agents
Escherichia coli
Inflammation
Injections
Wounds and Injuries

Keywords

  • MICROBIO
  • MOLIMMUNO

ASJC Scopus subject areas

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

Cite this

Host Inactivation of Bacterial Lipopolysaccharide Prevents Prolonged Tolerance Following Gram-Negative Bacterial Infection. / Lu, Mingfang; Varley, Alan W.; Ohta, Shoichiro; Hardwick, John; Munford, Robert S.

In: Cell Host and Microbe, Vol. 4, No. 3, 11.09.2008, p. 293-302.

Research output: Contribution to journalArticle

Lu, Mingfang ; Varley, Alan W. ; Ohta, Shoichiro ; Hardwick, John ; Munford, Robert S. / Host Inactivation of Bacterial Lipopolysaccharide Prevents Prolonged Tolerance Following Gram-Negative Bacterial Infection. In: Cell Host and Microbe. 2008 ; Vol. 4, No. 3. pp. 293-302.
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