Principles of Periodontology

Periodontal diseases are among the most common diseases affecting humans. Dental biofilm is a contributor to the etiology of most periodontal diseases. It is also widely accepted that immunological and inflammatory responses to biofilm components are manifested by signs and symptoms of periodontal disease. The outcome of such interaction is modulated by risk factors (modifiers), either inherent (genetic) or acquired (environmental), significantly affecting the initiation and progression of different periodontal disease phenotypes. While definitive genetic determinants responsible for either susceptibility or resistance to periodontal disease have yet to be identified, many factors affecting the pathogenesis have been described, including smoking, diabetes, obesity, medications, and nutrition. Currently, periodontal diseases are classified based upon clinical disease traits using radiographs and clinical examination. Advances in genomics, molecular biology, and personalized medicine may result in new guidelines for unambiguous disease definition and diagnosis in the future. Recent studies have implied relationships between periodontal diseases and systemic conditions. Answering critical questions regarding host‐parasite interactions in periodontal diseases may provide new insight in the pathogenesis of other biomedical disorders. Therapeutic efforts have focused on the microbial nature of the infection, as active treatment centers on biofilm disruption by non‐surgical mechanical debridement with antimicrobial and sometimes anti‐inflammatory adjuncts. The surgical treatment aims at gaining access to periodontal lesions and correcting unfavorable gingival/osseous contours to achieve a periodontal architecture that will provide for more effective oral hygiene and periodontal maintenance. In addition, advances in tissue engineering have provided innovative means to regenerate/repair periodontal defects, based upon principles of guided tissue regeneration and utilization of growth factors/biologic mediators. To maintain periodontal stability, these treatments need to be supplemented with long‐term maintenance (supportive periodontal therapy) programs

TLR4 and NKT Cell Synergy in Immunotherapy against Visceral Leishmaniasis

NKT cells play an important role in autoimmune diseases, tumor surveillance, and infectious diseases, providing in most cases protection against infection. NKT cells are reactive to CD1d presented glycolipid antigens. They can modulate immune responses by promoting the secretion of type 1, type 2, or immune regulatory cytokines. Pathogen-derived signals to dendritic cells mediated via Toll like Receptors (TLR) can be modulated by activated invariant Natural Killer T (iNKT) cells. The terminal β-(1–4)-galactose residues of glycans can modulate host responsiveness in a T helper type-1 direction via IFN-γ and TLRs. We have attempted to develop a defined immunotherapeutic, based on the cooperative action of a TLR ligand and iNKT cell using a mouse model of visceral leishmaniasis. We evaluated the anti-Leishmania immune responses and the protective efficacy of the β-(1–4)-galactose terminal NKT cell ligand glycosphingophospholipid (GSPL) antigen of L. donovani parasites. Our results suggest that TLR4 can function as an upstream sensor for GSPL and provoke intracellular inflammatory signaling necessary for parasite killing. Treatment with GSPL was able to induce a strong effective T cell response that contributed to effective control of acute parasite burden and led to undetectable parasite persistence in the infected animals. These studies for the first time demonstrate the interactions between a TLR ligand and iNKT cell activation in visceral leishmaniasis immunotherapeutic

Tumorigenic Potential of Mononucleated Small Cells of Hodgkin Lymphoma Cell Lines

Tumor cells with tumorigenic potential are limited to a small cell population known as cancer stem cells (CSCs). CSCs yield both CSCs and non-CSCs, whereas non-CSCs do not yield CSCs. CSCs have not been identified in any malignant lymphomas. Hodgkin lymphoma (HL) is a mostly B-cell neoplasm that can be diagnosed by the presence of multinucleated (Reed-Sternberg; RS) cells admixed with Hodgkin cells with distinct nucleoli and various inflammatory cells. Here, the tumorigenic potential of cells with a single nucleus (S) and cells with multiple nuclei (M), which may be equivalent to Hodgkin and RS cells, respectively, was examined in HL cell lines L1236 and L428. Cultures of single S cells yielded both S and M cells, whereas M cell cultures yielded only M cells. When either cultured in methylcellulose or inoculated into NOD/SCID mice, the colony number and tumor size were both larger in S than in M cells. Concentrations of intracellular reactive oxygen species (ROS) were at low levels in a portion of S cells that abundantly expressed FoxO3a, a transcription factor that regulates ROS-degrading enzymes. In clinical samples of HL, FoxO3a was expressed in mononuclear Hodgkin cells but not in multinucleated RS cells. These findings suggest that smaller cells or Hodgkin cells that show low-ROS concentrations and high FoxO3a expression levels might be candidates for HL CSCs