Impact of LL-37 on anti-infective immunity Dawn M. E. Bowdish * , Donald J. Davidson * ,2 , Y. Elaine Lau * , Ken Lee † , Monisha G. Scott † and Robert E. W. Hancock * ,1 * Centre for Microbial Diseases and Immunity Research; and † Inimex Pharmaceuticals Inc., Vancouver, British Columbia, Canada 1 Correspondence: Centre for Microbial Diseases and Immunity Research, University of British Columbia, 2259 Lower Mall Research Station, Vancouver, British Columbia V6T 1Z4, Canada. E-mail: bob@cmdr.ubc.ca 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. Key Words: cathelicidin • host defense peptide • immunomodulator • innate immunity
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Impact of LL-37 on anti-infective immunity
Bowdish, Dawn M. E.; Davidson, Donald J.; Lau, Y. Elaine; Lee, Ken; Scott, Monisha G.; Hancock, Robert E. W.
Follow Journal of Leukocyte Biology
, Volume 77 (4): 451
Fed of American Socs for Experimental Biology – Apr 1, 2005
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