Table 1.

Immunomodulatory properties of mammalian host defense peptides

Cell or tissue type	Peptide production and activity	References
Hematopoietic cells
Monocytes and macrophages	LL-37 and β-defensins are monocyte chemoattractants in vitro and in vivo. LL-37 has anti-endotoxic activity, induces chemokine production, promotes IL-1β secretion, but inhibits inflammatory responses to certain TLR ligands	32, 61, 62
Neutrophils	LL-37 and defensins are produced by neutrophils, stored within neutrophil granules and play an important microbicidal role in phagolysosomes. When released extracellularly, LL-37 acts as a neutrophil chemoattractant, inhibits neutrophil apoptosis, reduces pro-inflammatory cytokines and promotes both chemokine induction and the antimicrobial functions of neutrophils	63, 64
Mast cells	Mast cells are important producers of LL-37 in the skin. LL-37 and β-defensins are mast cell chemoattractants and promote mast cell degranulation	65, 66
Conventional dendritic cells	Defensins and cathelicidins are dendritic cell (DC) chemoattractants. LL-37 promotes differentiation of monocyte-derived DCs, but inhibits DC maturation and activation by TLR-ligands. β-Defensin 2 might promote DC activation as an endogenous TLR4 ligand. The adjuvant activities of defensins and cathelicidins in vivo might be mediated in part through their activity on DCs	67, 68, 69
Plasmacytoid dendritic cells	LL-37 in complex with DNA oligonucleotides strongly induces IFNα production by plasmacytoid DCs. This activity might contribute to the pathology of psoriasis	[70]
Epithelial cells
Keratinocytes	LL-37 promotes keratinocyte migration and production of IL-8, inhibits keratinocyte apoptosis, modulates responses to TLR ligands, and might have wound healing activities in the skin. Altered proteolytic processing of hCAP18 and LL-37 has been implicated in the pathology of rosacea	54, 71, 72
Bronchial epithelium	LL-37 acts on bronchial epithelial cells to stimulate cytokine and chemokine production and promote apoptosis	73, 74
Intestinal epithelium	α-Defensins are produced by Paneth cells and their microbiocidal activity plays an important role in the immune defenses of the gut. Reduced α-defensin production might contribute to Crohn's disease. LL-37 promotes mucin production and survival of intestinal epithelial cells	75, 76
Other cells
Vascular endothelium	LL-37 induces activation and proliferation of vascular endothelium, promoting angiogenesis	[77]
Mesenchymal stromal cells	LL-37 acts as a chemokine for mesenchymal stromal cells and promotes the production of various cytokines, as well as VEGF and MMP2; this can contribute to angiogenesis and tumor progression	[57]
Cancer cells	LL-37 promotes migration and proliferation of lung, ovarian and breast cancer cells and LL-37 production by cancer cells in vivo promotes tumor growth. However, LL-37 also augments the anti-cancer therapeutic activity of CpG oligonucleotides	78, 79