Chapter 19 : Antimicrobial Peptides as Mucosal Adjuvants

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This chapter briefly reviews the major classes and types of conventional adjuvants. It then reviews the use of antimicrobial peptides as adjuvants and examines the ability of antimicrobial peptides, including defensins, to augment and direct an immune response to coadministered antigens. An emulsion of mineral oil and killed mycobacteria is called Freund’s complete adjuvant and is one of the most potent adjuvants known for stimulating both humoral and cellular immune responses. Even microbial toxins, like heat-labile enterotoxin and toxin, are potent mucosal adjuvants. Antimicrobial peptides are a unique and diverse group of molecules produced by many cell types and tissues throughout the Eukarya. Antimicrobial peptides are divided into groups based on their biochemical compositions and structures. Some antimicrobial peptides are reported to have immunomodulatory and adjuvant activities. Cathelin-related antimicrobial peptide (CRAMP) induces humoral and cellular antigen-specific immune responses to ovalbumin in mice in a dose-dependent manner. Some antimicrobial peptides have been reported previously to have potent adjuvant activity in tumor immunotherapy. Microorganisms coming in contact with epithelial cells will induce the production of defensins and cytokines. Ideally, defensins would recruit immature dendritic cells, T cells, and B cells to local sites, promote antigen uptake and processing by dendritic cells, and increase the immunogenicity of the coadministered antigen.

Citation: Pingel L, Lu X, Brogden K. 2007. Antimicrobial Peptides as Mucosal Adjuvants, p 281-295. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch19
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Human neutrophil peptide α-defensins, human β-defensins, and cathelicidins (e.g., LL-37) are very prevalent in both the oronasal cavity and respiratory tract mucosa ( ) and mucosal secretions ( ) and are ideally positioned at these portals to interact with an extensive and diverse group of microbial antigens. GCF, gingival crevicular fluid; PMN, polymorphonuclear leukocytes.

Citation: Pingel L, Lu X, Brogden K. 2007. Antimicrobial Peptides as Mucosal Adjuvants, p 281-295. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch19
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Image of FIGURE 2

The presence of normal commensals (A) or pathogens (B) induces the differential expression of human β-defensins (HBD-1, HBD-2, HBD-3, and HBD-4) by mucosal epithelial cells or induces the expression of IL-8, which attracts polymorphonuclear leukocytes, a likely source of human neutrophil peptide (HNP-1, HNP-2, HNP-3, HNP-4) α-defensins. These defensins are available to interact with microorganisms or their microbial products (step 1). This interaction enhances the adaptive immune response to the microbial antigen (steps 2 to 4). Ag, antigen. Adapted from ( ) with permission of the publisher.

Citation: Pingel L, Lu X, Brogden K. 2007. Antimicrobial Peptides as Mucosal Adjuvants, p 281-295. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch19
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Types of adjuvants from nonbacterial sources

Citation: Pingel L, Lu X, Brogden K. 2007. Antimicrobial Peptides as Mucosal Adjuvants, p 281-295. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch19
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Types of adjuvants derived from bacteria

Citation: Pingel L, Lu X, Brogden K. 2007. Antimicrobial Peptides as Mucosal Adjuvants, p 281-295. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch19
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Cytokines used as immunological adjuvants

Citation: Pingel L, Lu X, Brogden K. 2007. Antimicrobial Peptides as Mucosal Adjuvants, p 281-295. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch19
Generic image for table

Antimicrobial peptides used as immunological adjuvants

Citation: Pingel L, Lu X, Brogden K. 2007. Antimicrobial Peptides as Mucosal Adjuvants, p 281-295. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch19

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