The Cationic Antimicrobial Peptide LL-37 Modulates Dendritic Cell Differentiation and Dendritic Cell-Induced T Cell Polarization

Davidson, Donald J.; Currie, Antony; Reid, Gregor S. D.; Bowdish, Dawn M. E.; MacDonald, Kelly L.; Carter, Rebecca; Hancock, Robert E. W.; Speert, David P.

doi:10.4049/jimmunol.172.2.1146

Cited by 370 publications

(240 citation statements)

References 46 publications

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“…This effect appears to be mediated by the P2X receptor. LL-37 also influences dendritic cell differentiation and dendritic cell induced T cell polarization [147]. Dendritic cells generated from blood monocytes under the influence of LL-37 have significantly up-regulated endocytotic capacity, modified expression of phagocytic receptors, enhanced costimulatory molecule expression and secretion of Th-1-inducing cytokines [147].…”

Section: Role Of Amps In Inflammation Angiogenesis and Regulation Omentioning

confidence: 99%

Functions of Antimicrobial Peptides in Host Defense and Immunity

Beißwenger¹,

Bals

2005

CPPS

102

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Antimicrobial peptides (AMPs) are effector molecules of the innate immune system. AMPs have a broad antimicrobial spectrum and lyse microbial cells by interaction with biomembranes. Besides their direct antimicrobial function, they have multiple roles as mediators of inflammation with impact on epithelial and inflammatory cells influencing diverse processes such as cytokine release, cell proliferation, angiogenesis, wound healing, chemotaxis, immune induction, and protease-antiprotease balance. Furthermore, AMPs qualify as prototypes of innovative drugs that may be used as antibiotics, anti-lipopolysaccharide drugs, or modifiers of inflammation. This review summarizes the current knowledge about the basic and applied biology of antimicrobial peptides and discusses features of AMPs in host defense and inflammation.

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Section: Role Of Amps In Inflammation Angiogenesis and Regulation Omentioning

confidence: 99%

Functions of Antimicrobial Peptides in Host Defense and Immunity

Beißwenger¹,

Bals

2005

CPPS

102

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“…Human HDP LL-37 is a potent modifier of DC differentiation from circulating hematopoietic precursor cells and pre-DCs (monocytes and plasmacytoid cells) and can influence adaptive immunity by interaction with iDCs [25,26]. LL-37 up-regulates the endocytic capacity of iDCs, modifies the expression of phagocytic receptors and enhances the secretion of Th1-inducing cytokines in mature DCs [26].…”

Section: Diverse Immunity-related Biological Effectsmentioning

confidence: 99%

Cationic Host Defence Peptides: Multifaceted Role in Immune Modulation and Inflammation

2012

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Host defence peptides (HDPs) are innate immune effector molecules found in diverse species. HDPs exhibit a wide range of functions ranging from direct antimicrobial properties to immunomodulatory effects. Research in the last decade has demonstrated that HDPs are critical effectors of both innate and adaptive immunity. Various studies have hypothesized that the antimicrobial property of certain HDPs may be largely due to their immunomodulatory functions. Mechanistic studies revealed that the role of HDPs in immunity is very complex and involves various receptors, signalling pathways and transcription factors. This review will focus on the multiple functions of HDPs in immunity and inflammation, with special reference to cathelicidins, e.g. LL-37, certain defensins and novel synthetic innate defence regulator peptides. We also discuss emerging concepts of specific HDPs in immune-mediated inflammatory diseases, including the potential use of cationic peptides as therapeutics for immune-mediated inflammatory disorders.

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“…Collectively, these results show that LL-37 may inhibit inflammatory responses to microbial stimuli, but may also act as a proinflammatory mediator. In addition, its ability to affect differentiation of dendritic cells [21] and chemotaxis of monocytes and T cells [2], its angiogenic activity [22] and its involvement in epithelial wound healing [23] suggest that LL-37 may also be involved in adaptive immunity and wound repair.…”

Section: Introductionmentioning

confidence: 99%

Human Cathelicidin LL-37 Is a Chemoattractant for Eosinophils and Neutrophils That Acts via Formyl-Peptide Receptors

Tjabringa

Ninaber²,

Drijfhout³

et al. 2006

Int Arch Allergy Immunol

211

166

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Background: Inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are characterized by the presence of eosinophils and neutrophils. However, the mechanisms that mediate the influx of these cells are incompletely understood. Neutrophil products, including neutrophil elastase and antimicrobial peptides such as neutrophil defensins and LL-37, have been demonstrated to display chemotactic activity towards cells from both innate and adaptive immunity. However, chemotactic activity of LL-37 towards eosinophils has not been reported. Therefore, the aim of the present study was to investigate the chemotactic activity of LL-37 for eosinophils and to explore the mechanisms involved in LL-37-mediated attraction of neutrophils and eosinophils. Methods: Neutrophils and eosinophils were obtained from venous blood of healthy donors. Chemotaxis was studied using a modified Boyden chamber technique. Involvement of formyl-peptide receptors (FPRs) was studied using the antagonistic peptide tBoc-MLP. Activation of the mitogen-activated protein kinase (MAPK) ERK1/2 was studied by Western blotting using antibodies directed against phosphorylated ERK1/2. Results: Our results show that LL-37 chemoattracts both eosinophils and neutrophils. The FPR antagonistic peptide tBoc-MLP inhibited LL-37-induced chemotaxis. Whereas the FPR agonist fMLP activated ERK1/2 in neutrophils, LL-37 did not, indicating that fMLP and LL-37 deliver different signals through FPRs. Conclusions: LL-37 displays chemotactic activity for eosinophils and neutrophils, and this activity is mediated via an FPR. These results suggest that LL-37 may play a role in inflammatory lung diseases such as asthma and COPD.

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The Cationic Antimicrobial Peptide LL-37 Modulates Dendritic Cell Differentiation and Dendritic Cell-Induced T Cell Polarization

Cited by 370 publications

References 46 publications

Functions of Antimicrobial Peptides in Host Defense and Immunity

Functions of Antimicrobial Peptides in Host Defense and Immunity

Cationic Host Defence Peptides: Multifaceted Role in Immune Modulation and Inflammation

Human Cathelicidin LL-37 Is a Chemoattractant for Eosinophils and Neutrophils That Acts via Formyl-Peptide Receptors

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