CLP-induced impairment of innate immune function is caused by exposure to the cecal lumenal contents and not the tissue trauma or tissue ischemia/necrosis components

Microbes Infect. 2012 Jan;14(1):35-42. doi: 10.1016/j.micinf.2011.08.002. Epub 2011 Aug 30.

Abstract

When mice are subjected to a Pseudomonas aeruginosa challenge 5 days after cecal ligation and puncture (CLP), clearance of the Pseudomonas is diminished when compared to sham mice. The object of this study was to determine which component(s) of CLP contributed to the impairment of the innate immune response. Mice subjected to either trauma alone or cecal ischemia/necrosis alone did not have impaired ability to clear a subsequent Pseudomonas challenge (determined by colony-forming units (cfu's) after culture of spleen tissue). However, mice subjected to abdominal contamination with heat-killed cecal contents had reduced ability to clear the subsequent Pseudomonas challenge. In contrast to normobiotic mice, neither CLP performed in germ-free mice nor abdominal contamination of mice with cecal contents from germ-free mice adversely affected clearance of a subsequent Pseudomonas challenge. These data suggest that suppressed immune function after CLP is due to exposure to microbial ligands within the cecal lumen rather than tissue trauma, ischemia, or necrosis. However, suppression of immune function did not appear to be due to exposure to LPS as TLR4-deficient mice subject to abdominal contamination with cecal contents had diminished clearance of a Pseudomonas challenge similar to that seen in wild-type mice.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacteremia / blood
  • Bacteremia / immunology*
  • Bacteremia / microbiology
  • Cecum / blood supply
  • Cecum / immunology*
  • Cecum / injuries
  • Cecum / microbiology
  • Disease Models, Animal
  • Germ-Free Life
  • Humans
  • Immunity, Innate
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Ischemia / blood
  • Ischemia / immunology
  • Ligands
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pseudomonas Infections / blood
  • Pseudomonas Infections / immunology*
  • Pseudomonas aeruginosa / immunology*
  • Wounds and Injuries / blood
  • Wounds and Injuries / immunology

Substances

  • Ligands
  • Interleukin-10
  • Interferon-gamma