The severity of periodontal disease is dependent on a combination of host, microbial agent, and environmental factors. One strong correlate related to periodontal disease pathogenesis is the immune status of the host. Our approach to improve the immune status is to use human neutrophil peptide (HNP) defensins or human beta-defensins (HBD), elements of innate host defense, to initiate and regulate the adaptive immune response to foreign antigens. In this Plan, we posit that HNP or HBD, co-administered with Porphyromonas gingivalis antigens to oronasal mucosal surfaces, regulates the adaptive immune response resulting in class switching of antibodies to high avidity isotypes. Results from this work will not only provide fundamental information on the regulating role of defensins in generating adaptive immune responses to various bacterial antigens in the oral cavity but specific preliminary evidence on ways to direct an adaptive immune response to select P. gingivalis antigens that would likely hinder the pathogenesis of periodontal disease and lessen associated inflammation and tissue damage caused by this organism. The following Aims are proposed: 1) to determine if defensins induce an adaptive immune response to bacterial antigens. Preliminary studies suggest that defensins, co-administered intranasally with ovalbumin, induced different antibody isotype, interferon-gamma, and interleukin profiles that were unique to the individual defensin used. We will use hemagglutinin B of P. gingivalis, one of the leading etiologic agents of periodontal disease, as the antigen to assess the ability of defensins to induce a similar response. 2) to assess the nature of the defensin-antigen interaction and the conditions necessary for induced adaptive immunity. We will also use the capsular polysaccharide and fimbrial antigen of P. gingivalis to determine if the nature of the antigen influences the ability of defensins to induce an adaptive immune response. 3) To determine the defensin domain necessary for dendritic cell chemotaxis and activation. HBD2 is chemotactic for immature dendritic cells and may initiate the mechanism for defensin-induced adaptive immunity to microbial antigens. Preliminary studies suggest that HBDs can chemoattract murine dendritic cells, and we will use this assay to determine the chemotactic domain of HBDs and the conditions of HBD-hemagglutinin B interaction.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Oral Biology and Medicine Subcommittee 1 (OBM)
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Lunsford, Dwayne
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University of Iowa
Schools of Dentistry
Iowa City
United States
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Bates, Amber M; Gomez Hernandez, Maria Paula; Lanzel, Emily A et al. (2018) Matrix metalloproteinase (MMP) and immunosuppressive biomarker profiles of seven head and neck squamous cell carcinoma (HNSCC) cell lines. Transl Cancer Res 7:533-542
Garaicoa, Jorge L; Fischer, Carol L; Bates, Amber M et al. (2018) Promise of Combining Antifungal Agents in Denture Adhesives to Fight Candida Species Infections. J Prosthodont 27:755-762
Raina, Monica; Bates, Amber M; Fischer, Carol L et al. (2018) Human beta defensin 3 alters matrix metalloproteinase production in human dendritic cells exposed to Porphyromonas gingivalis hemagglutinin B. J Periodontol 89:361-369
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Fischer, Carol L; Dawson, Deborah V; Blanchette, Derek R et al. (2016) Protein Analysis of Sapienic Acid-Treated Porphyromonas gingivalis Suggests Differential Regulation of Multiple Metabolic Pathways. J Bacteriol 198:157-67
Lanzel, Emily A; Paula Gomez Hernandez, M; Bates, Amber M et al. (2016) Predicting PD-L1 expression on human cancer cells using next-generation sequencing information in computational simulation models. Cancer Immunol Immunother 65:1511-1522
Mehalick, Leslie A; Poulsen, Christopher; Fischer, Carol L et al. (2015) Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells. Data Brief 5:285-91

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