Cathelicidin antimicrobial peptides block dendritic cell TLR4 activation and allergic contact sensitization.
Cathelicidins are antimicrobial peptides of the innate immune system that establish an antimicrobial barrier at epithelial interfaces and have been proposed to have a proinflammatory function. We studied the role of cathelicidin in allergic contact dermatitis, a model requiring dendritic cells of the innate immune response and T cells of the adaptive immune response. Deletion of the murine cathelicidin gene Cnlp enhanced an allergic contact response, whereas local administration of cathelicidin before sensitization inhibited the allergic response. Cathelicidins inhibited TLR4 but not TLR2 mediated induction of dendritic cell maturation and cytokine release, and this inhibition was associated with an alteration of cell membrane function and structure. Further analysis in vivo connected these observations because inhibition of sensitization by exogenous cathelicidin was dependent on the presence of functional TLR4. These observations provide evidence that cathelicidin antimicrobial peptides mediate an anti-inflammatory response in part by their activity at the membrane.
Di Nardo
Anna
A
Division of Dermatology, Department of Medicine, University of California, San Diego, CA 92161, USA.
Braff
Marissa H
MH
Taylor
Kristen R
KR
Na
Changrim
C
Granstein
Richard D
RD
McInturff
Jamie E
JE
Krutzik
Stephan
S
Modlin
Robert L
RL
Gallo
Richard L
RL
D000818:Animals; D000893:Anti-Inflammatory Agents; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D016207:Cytokines; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D007109:Immunity; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism*; D054804:Cathelicidins
D000893:Anti-Inflammatory Agents; D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D054804:Cathelicidins