Impact of LL-37 on anti-infective immunity

Dawn M.E. Bowdish, Donald J. Davidson, Y. Elaine Lau, Ken Lee, Monisha G. Scott, Robert E.W. Hancock

Research output: Contribution to journalArticle

276 Citations (Scopus)

Abstract

Host defense peptides (often called cationic antimicrobial peptides) have pleiotropic immunomodulatory functions. The human host defense peptide LL-37 is up-regulated at sites of infection and has little or no antimicrobial activity in tissue-culture media but under the same conditions, demonstrates immunomodulatory effects on epithelial cells, monocytes, and dendritic cells (DC). These effects include the induction of chemokine production in a mitogen-activated protein kinase-dependent manner in epithelial cell lines and monocytes and profound alterations of DC differentiation, resulting in the capacity to enhance a T helper cell type 1 response. Although the exact mechanisms of interaction between LL-37 and these cell types have not been elucidated, there is evidence for specific (i.e., receptor-mediated) and nonspecific interactions. The relative significance of the direct antimicrobial activities and immunomodulatory properties of LL-37 and other cationic host defense peptides in host defense remains unresolved. To demonstrate that antimicrobial activity was not necessarily required for protection in vivo, model peptides were synthesized and tested for antimicrobial and immunomodulatory activities. A peptide with no antimicrobial activity was found to be protective in animal models of Staphylococcus aureus and Salmonella infection, implying that a host defense peptide can protect by exerting immunomodulatory properties.

Original languageEnglish
Pages (from-to)451-459
Number of pages9
JournalJournal of Leukocyte Biology
Volume77
Issue number4
DOIs
Publication statusPublished - 1 Apr 2005
Externally publishedYes

Keywords

  • Cathelicidin
  • Host defense peptide
  • Immunomodulator
  • Innate immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this

Bowdish, D. M. E., Davidson, D. J., Lau, Y. E., Lee, K., Scott, M. G., & Hancock, R. E. W. (2005). Impact of LL-37 on anti-infective immunity. Journal of Leukocyte Biology, 77(4), 451-459. https://doi.org/10.1189/jlb.0704380