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Cathelicidin mediates innate intestinal defense against colonization with epithelial adherent bacterial pathogens

Mitsutoshi Iimura1, Richard L Gallo, Koji Hase

  • 1Department of Medicine, University of California at San Diego, La Jolla, CA 92093-0623, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|April 9, 2005
PubMed

Insights

The murine cathelicidin (mCRAMP) peptide defends the colon against bacterial infections. Mice lacking mCRAMP showed increased susceptibility to Citrobacter rodentium, highlighting its role in innate immunity.

Area of Science:

  • Microbiology
  • Immunology
  • Genetics

Background:

  • Cathelicidins are antimicrobial peptides crucial for innate immunity.
  • Murine cathelicidin-related antimicrobial peptide (mCRAMP) is encoded by the Cnlp gene.
  • mCRAMP expression is primarily observed in colon surface epithelial cells.

Purpose of the Study:

  • To investigate the role of mCRAMP in innate antimicrobial defense within the murine colon.
  • To assess the antimicrobial activity of mCRAMP against the enteric pathogen Citrobacter rodentium.
  • To evaluate the susceptibility of mCRAMP-deficient mice to C. rodentium infection.

Main Methods:

  • Analyzing mCRAMP expression patterns in the colon.
  • Testing the antimicrobial activity of synthetic mCRAMP against C. rodentium.
  • Comparing C. rodentium infection outcomes in wild-type (Cnlp+/+) and knockout (Cnlp-/-) mice.
  • Assessing epithelial cell damage and bacterial dissemination in infected mice.

Main Results:

  • Synthetic mCRAMP demonstrated antimicrobial activity against C. rodentium.
  • Colon extracts from Cnlp+/+ mice exhibited greater antimicrobial activity than those from Cnlp-/- mice.
  • Cnlp-/- mice showed increased C. rodentium colonization, epithelial damage, and systemic infection compared to Cnlp+/+ mice.
  • Cnlp+/+ mice were protected against C. rodentium infection doses that were lethal to Cnlp-/- mice.

Conclusions:

  • Cathelicidin plays a significant role in the innate antimicrobial defense of the colon.
  • mCRAMP is essential for protecting the colon epithelium against enteric bacterial pathogens like C. rodentium.
  • Targeting cathelicidin pathways could offer therapeutic strategies against intestinal infections.

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