Antimicrobial Peptides as Mucosal Adjuvants

Pingel, Lindsey C.; Lü, Xiaoying; Brogden, Kim A.

doi:10.1128/9781555815851.ch19

Cited by 4 publications

(6 citation statements)

References 113 publications

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“…HNP1 and HBD3 enhance a serum IgG response to rHagB, and HNP2 and HBD3 enhance the IgG antibody responses in BALF and serum to rFimA. These results confirm and extend our previous results and those of others demonstrating that HBD3 and HNP1 and 2 can bind to rHagB and rFimA, HBD3 can attenuate proinflammatory cytokine responses of human myeloid dendritic cells exposed to rHagB, and HNP1–3 and HBD1 and 2 can enhance antibody responses to coadministered antigens [18,19,21,22,24]. We noted that intranasal administration of HNPs, HBDs or PBS alone to mice did not induce significant proinflammatory cytokine responses in mucosal fluids or serum.…”

Section: Discussionsupporting

confidence: 90%

“…Previous studies assessed the ability of HNPs and HBDs to enhance the antibody responses to intranasal administration of ovalbumin [18,19,21,22,24] and this study assessed the ability of HNPs and HBDs to attenuate cytokine and chemokine responses and to enhance the antibody responses to intranasal administration of rHagB and rFimA. CD4 + Th cells are classified as Th1, Th2 and Th17 based on their cytokine expression profile and, in our first study, rHagB induced the production of IL-6 and KC in nasal lavage fluid of mice, a cytokine expression profile characteristic of a Th17 response.…”

Section: Discussionmentioning

confidence: 99%

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Defensins Attenuate Cytokine Responses Yet Enhance Antibody Responses to Porphyromonas Gingivalis Adhesins in Mice

et al. 2009

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Aim-Our aim is to assess the ability of human neutrophil peptide α-defensins (HNPs) and human β-defensins (HBDs) to attenuate proinflammatory cytokine responses and enhance antibody responses to recombinant hemagglutinin B (rHagB) or recombinant fimbrillin A (rFimA) from Porphyromonas gingivalis 381 in mice.Materials & methods-In the first study, C57BL/6 mice were given 10 μg rHagB or rFimA without and with 1 μg HNP1, HNP2, HBD1, HBD2 or HBD3. At 24 h, mice were euthanized and cytokine concentrations were determined in nasal wash fluid (NWF), bronchoalveolar lavage fluids, saliva and serum. In the second study, C57BL/6 mice were given 10 μg rHagB or rFimA without and with 1 μg HNPs or HBDs similarly on days 0, 7 and 14. At 21 days, mice were euthanized and rHagB-and rFimA-specific antibody responses were determined in NWF, bronchoalveolar lavage fluids, saliva and serum.Results-Mice given rHagB + HNP2, rHagB + HBD1 and rHagB + HBD3 produced significantly lower (p < 0.05) IL-6 responses than mice given rHagB alone. Mice given rHagB + HNP1, rHagB + HNP2, rHagB + HBD1 and rHagB + HBD3 produced significantly lower (p < 0.05) keratinocytederived chemokine responses than mice given rHagB alone. Mice given rFimA produced very low levels of IL-6 and only moderate levels of keratinocyte-derived chemokine in NWF that were not attenuated by prior incubation of rFimA with any defensin. Mice given rHagB + HNP1 produced a significantly higher (p < 0.05) serum IgG antibody response than mice given rHagB alone and mice given rFimA + HNP2 produced a higher, but not significant, antibody response. Conclusion-The ability of HNPs andHBDs to attenuate proinflammatory cytokine responses in murine NWF and enhance IgG antibody responses in serum was dependent upon both the defensin and antigen of P. gingivalis. Keywords defensins; fimbriae A; hemagglutinin B; immunity; Porphyromonas gingivalisDefensins are small, host-derived peptides with broad antimicrobial activity against Gramnegative and Gram-positive bacteria, fungi and enveloped viruses [1][2][3][4]. In humans, there are human neutrophil peptide α-defensins (HNPs), human θ-defensins (HBDs) and human θdefensins. HNPs are found in neutrophil granules, macrophages, mucosal crypt cells and Paneth cells and contain 29-35 amino acids. HNP1-4 are found in azurophil granule fractions of human neutrophils and human defensins (HD)5 and 6 are found in human Paneth cells. HBDs are expressed in epithelia of many organs and in nonepithelial tissues [5][6][7][8][9]. The latter tissues include articular cartilage, synovial membranes and bone [10][11][12]. HBDs contain 36-45 amino acids. Although 28 β-defensin genes have been described in humans, HBD1-4 are among the more closely studied HBDs.Defensins regulate innate immune mechanisms [3,13]. In addition to their antimicrobial activity, they chemoattract CD4/CD45 RA + cells, CD8 + T cells, monocytes and immature dendritic cells, enhance phagocytosis by macrophages, activate and degranulate mast cells; regulate cytokine production, regulate comp...

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Defensins Attenuate Cytokine Responses Yet Enhance Antibody Responses to Porphyromonas Gingivalis Adhesins in Mice

et al. 2009

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“…Many antimicrobial peptides have the properties of classical adjuvants and elicit enhanced humoral and or cellular immune responses against tumor antigens, protein antigens and even microbial antigens [41,58]. Enhanced immune responses occur with mixtures (containing antimicrobial peptides and antigens), conjugates (containing antimicrobial peptide coupled to antigens) and fusion proteins (containing expressed antimicrobial peptides and antigens).…”

Section: Defensins Enhance Adaptive Immunitymentioning

confidence: 99%

“…For a comprehensive list of adjuvants, see the review articles by Pingel et al [58] and Guy [59]. These substances include: nonbacterial adjuvants containing minerals, synthetic polymers, polyanions, or hydrophobic or amphipathic substances [60–62]; bacterial adjuvants consisting of whole bacteria, LPS, peptidoglycan fragments, DNA, toxins or other cellular components from Gram-positive bacteria, Gram-negative bacteria or Mycobacteria species [63–66]; and cytokines, costimulatory agonists, and antimicrobial peptides and proteins [67–70].…”

Section: Defensins Enhance Adaptive Immunitymentioning

confidence: 99%

Defensins as Anti-Inflammatory Compounds and Mucosal Adjuvants

et al. 2009

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Human neutrophil peptide α-defensins and human β-defensins are small, well-characterized peptides with broad antimicrobial activities. In mixtures with microbial antigens, defensins attenuate proinflammatory cytokine responses by dendritic cells in culture, attenuate proinflammatory cytokine responses in the nasal fluids of exposed mice and enhance antibody responses in the serum of vaccinated mice. Although the exact mechanisms are unknown, defensins first start by binding to microbial antigens and adhesins, often attenuating toxic or inflammatory-inducing capacities. Binding is not generic; it appears to be both defensin-specific and antigen-specific with high affinities. Binding of defensins to antigens may, in turn, alter the interaction of antigens with epithelial cells and antigen-presenting cells attenuating the production of proinflammatory cytokines. The binding of defensins to antigens may also facilitate the delivery of bound antigen to antigenpresenting cells in some cases via specific receptors. These interactions enhance the immunogenicity of the bound antigen in an adjuvant-like fashion. Future research will determine the extent to which defensins can suppress early events in inflammation and enhance systemic antibody responses, a very recent and exciting concept that could be exploited to develop therapeutics to prevent or treat a variety of oral mucosal infections, particularly where inflammation plays a role in the pathogenesis of disease and its long-term sequelae.

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“…In this chapter, we present the alternate functions of peptides with antimicrobial activity, a topic of a number of excellent comprehensive reviews (Yang et al , 2002Pingel et al 2007 ;Rehaume and Hancock 2008 ;Semple et al 2010 ;Semple and Dorin 2012 ;Greer et al 2013 ). We start by presenting the roles of antimicrobial peptides in innate immunity and their ability to chemoattract and activate cells (Table 9.1 ).…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial Peptides in Host Defense: Functions Beyond Antimicrobial Activity

Brogden

Bates

Fischer

2015

Antimicrobial Peptides

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Antimicrobial peptides are well known for their important roles in host defense by enhancing the barrier function and limiting microbial populations of the skin and mucosa. However, many of these peptides are now known to have additional roles assisting innate and adaptive immune functions. To facilitate innate immunity, antimicrobial peptides activate complement, chemoattract cells (e.g., monocytes, macrophages, T cells, neutrophils, immature dendritic cells, and mast cells), enhance phagocytosis, and modulate the production of chemokines and proinfl ammatory cytokines in other cells. At local sites of initiation, antimicrobial peptides can act as opsonins to enhance phagocytosis by monocytes and phagocytes and can activate cells. In the latter, for example, treatment of osteoblasts and osteoblast-like MG63 cells with human beta-defensin (HBD)2 increases their proliferation rates. Treatment of osteoblast-like MG63 cells with HBD2 and HBD3 increases transcript levels of osteogenic markers for differentiation, increases antileukoprotease (ALP) levels, and enhances mineralized nodule formation. To facilitate adaptive immunity, antimicrobial peptides assist the uptake of antigens by monocytes or other antigen-presenting cells and later direct the process toward a Th1 or Th2 adaptive immune response. More commonly though, antimicrobial peptides induce a mixed response characterized by Th1-/Th2-specifi c antibodies and Th1/Th2 cytokines from antigen-exposed splenocytes of immunized animals. Finally, antimicrobial peptides can be detected in the margins around both oral and cutaneous wounds, and there is

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Antimicrobial Peptides as Mucosal Adjuvants

Cited by 4 publications

References 113 publications

Defensins Attenuate Cytokine Responses Yet Enhance Antibody Responses to Porphyromonas Gingivalis Adhesins in Mice

Defensins Attenuate Cytokine Responses Yet Enhance Antibody Responses to Porphyromonas Gingivalis Adhesins in Mice

Defensins as Anti-Inflammatory Compounds and Mucosal Adjuvants

Antimicrobial Peptides in Host Defense: Functions Beyond Antimicrobial Activity

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