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Chapter 18 : Effect of Defensins on Susceptibility to Infection at the Mucosal Surface

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Abstract:

Periodontal diseases are among the most common diseases of the oral cavity. Periodontal disease is the major cause of tooth loss in adults, and recently there has been increasing interest in the relationship of periodontal disease to important systemic diseases, such as cardiovascular disease and complications in pregnancy. Despite the importance of infection and colonization by bacteria and yeast in periodontal and candidal infections, the immune status of the host and the effectiveness of the host response are key determinants of disease susceptibility. The regulation of β-defensins by various mediators and their expression in oral tissues, salivary glands, and secretions suggest that β-defensins are in a prime position to defend epithelial cells and mucosa from infection and respond to inflammation in the periodontium. The complexity of multiple regulatory pathways involved in β-defensin expression and their physicochemical properties and structures supports their pluripotential functions. β-Defensin expression also appears to be regulated during inflammation in vivo. Unlike the results of in vitro studies demonstrating upregulation by inflammatory stimulants, such upregulation does not always occur in vivo. Understanding the basis for differential expression of β-defensins in the oral cavity will assist us in defining individuals at risk for periodontal diseases and infections.

Citation: Guthmiller J, Joly S. 2007. Effect of Defensins on Susceptibility to Infection at the Mucosal Surface, p 265-280. 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.ch18

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Figures

Image of FIGURE 1
FIGURE 1

Inducibility of HBD-1, HBD-2, and HBD-3 mRNA expression by cytokines (subject 316). mRNA expression stimulated by various cytokines and combinations of cytokines is seen for HBD-1 (panel A) using reverse transcription-PCR ( ) and real-time PCR ( ) and real-time PCR analysis for HBD-2 (panel B) and HBD-3 (panel C). The results from the cell line presented are typical of those seen for three additional subjects in whose cells the cytokines were tested. Each of the defensins demonstrates significant upregulation by individual cytokines and synergistic expression with select combinations of cytokines. Molecular sizes in base pairs are presented on each side of the gel in panel A. The GAPDH (glyceraldehyde-3-phosphate dehydrogenase) gene (421 bp) was used as a control housekeeping gene. Numbers in parentheses represent the amount (nanograms) used for the stimulations when more than one concentration was used for a particular cytokine. Asterisks indicate data that were significantly ( < 0.05) different from the control (medium alone). Error bars represent the standard error of the mean of triplicate measures. C+, HBD-1 cDNA-positive control. Reprinted from reference with permission.

Citation: Guthmiller J, Joly S. 2007. Effect of Defensins on Susceptibility to Infection at the Mucosal Surface, p 265-280. 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.ch18
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Image of FIGURE 2
FIGURE 2

Susceptibility of aerobic and anaerobic oral bacteria to HBD-2 and HBD-3. MICs, obtained from radial diffusion assays, of HBD-2 (A) and HBD-3 (B) for (), (), (), (), (), (), (), and () are shown. Values are means and standard deviations of triplicate assays.

Citation: Guthmiller J, Joly S. 2007. Effect of Defensins on Susceptibility to Infection at the Mucosal Surface, p 265-280. 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.ch18
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Tables

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TABLE 1

Differential induction of HBD-1, HBD-2, and HBD-3 by IL-1β, IFN-γ, and TNF-α as assessed by real-time PCR

Citation: Guthmiller J, Joly S. 2007. Effect of Defensins on Susceptibility to Infection at the Mucosal Surface, p 265-280. 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.ch18

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