Host Defense Peptides: Immune Modulation and Antimicrobial Activity In Vivo

  • Nicole J. Afacan
  • Laure M. Janot
  • Robert E. W. Hancock
Chapter
Part of the Progress in Inflammation Research book series (PIR)

Abstract

Cationic host defense peptides (HDPs), a vital component of the innate immune system, are amphipathic molecules of 12–50 amino acids in length and are produced by numerous cell types, either constitutively or in response to inflammatory stimuli. In addition to their antimicrobial and immunomodulatory properties, novel roles have been attributed to HDPs including promoting chemotaxis of immune cells, limiting inflammation/sepsis, promoting wound healing, regulating metabolism, and enhancing vaccine responses. These properties make HDPs a novel class of anti-infectives that can be exploited to treat immune and inflammatory disorders as well as infectious diseases. The emergence of multi-resistant bacteria is a major challenge facing modern healthcare since very few novel antibiotic agents are available. HDPs and their synthetic derivatives provide extremely valuable leads in the development of new treatment strategies for multi-resistant bacterial infections. This chapter reviews our basic knowledge on HDPs and synthetic cationic peptides and focuses on their current clinical application as anti-infectives, immunomodulators, and anticancer treatments. Challenges to their development as new therapeutics are also discussed.

Keywords

Host defense peptides Antimicrobial Immunomodulatory Cathelicidins Defensins Innate defense regulators 

Abbreviations

ATP

Adenosine triphosphate

BPI

Bactericidal/permeability-increasing protein

BMDC

Bone marrow-derived DCs

BRSV

Bovine respiratory syncytial virus

CAMP

Cathelicidin antimicrobial peptide

CDC

Centers for Disease Control and Prevention

CF

Cystic fibrosis

CFTR

Cystic fibrosis transmembrane conductance regulator

EGFR

Epidermal growth factor receptor

FDA

Food and Drug Administration

FMOC

Fluorenylmethoxycarbonyl

GAS

Group A Streptococcus

G-CSF

Granulocyte colony-stimulating factor

GM-CSF

Granulocyte-macrophages colony-stimulating factor

hst-5

Histatin 5

HDP

Host defense peptide

hBD

Human beta defensin

HIF-1α

Hypoxia-inducible factor-1α

HLA

Human leukocyte antigen

hLF

Human lactoferrin

HNP

Human neutrophil protein

Ig

Immunoglobulin

IDSA

Infectious Disease Society of America

IDR

Innate defense regulator

IOM

Institute of Medicine

IP-10

Interferon gamma-induced protein 10 kDa

IFN

Interferon

IL

Interleukin

LPS

Lipopolysaccharide

LTA

Lipoteichoic acid

MIP

Macrophage inflammatory protein

MC-1R

Melanocortin-1 receptor

MSH

Melanocyte-stimulating hormone

MRSA

Methicillin-resistant S. aureus strains

MCP

Monocyte chemotactic protein

ODN

Oligodeoxynucleotide

OVA

Ovalbumin

pDC

Plasmacytoid dendritic cell

PolyIC

Polyinosinic-polycytidylic acid

PP

Polyphosphazene

QSAR

Quantitative structure-activity relationship

RI

Retro-inverse

RNS

Reactive nitrogen species

ROS

Reactive oxygen species

TLR

Toll-like receptor

TNF

Tumor necrosis factor

VEGF

Vascular endothelial growth factor

Notes

Acknowledgments

The authors are grateful for the financial support provided by the Foundation for the National Institutes of Health, the Bill & Melinda Gates Foundation and the Canadian Institutes of Health Research through the Grand Challenges in Global Health initiative and Genome BC for the Pathogenomics of Innate Immunity research program. R.E.W. Hancock is the recipient of a Canada Research Chair. N.J. Afacan holds a studentship from the Natural Sciences and Engineering Research Council of Canada.

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Copyright information

© Springer Basel AG 2013

Authors and Affiliations

  • Nicole J. Afacan
    • 1
  • Laure M. Janot
    • 1
  • Robert E. W. Hancock
    • 1
  1. 1.Centre for Microbial Diseases and Immunity ResearchUniversity of British ColumbiaVancouverCanada

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