Direct Recognition of Fusobacterium nucleatum by the NK Cell Natural Cytotoxicity Receptor NKp46 Aggravates Periodontal Disease

Periodontitis is a common human chronic inflammatory disease that results in the destruction of the tooth attachment apparatus and tooth loss. Although infections with periopathogenic bacteria such as Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum) are essential for inducing periodontitis, the nature and magnitude of the disease is determined by the host's immune response. Here, we investigate the role played by the NK killer receptor NKp46 (NCR1 in mice), in the pathogenesis of periodontitis. Using an oral infection periodontitis model we demonstrate that following F. nucleatum infection no alveolar bone loss is observed in mice deficient for NCR1 expression, whereas around 20% bone loss is observed in wild type mice and in mice infected with P. gingivalis. By using subcutaneous chambers inoculated with F. nucleatum we demonstrate that immune cells, including NK cells, rapidly accumulate in the chambers and that this leads to a fast and transient, NCR1-dependant TNF-α secretion. We further show that both the mouse NCR1 and the human NKp46 bind directly to F. nucleatum and we demonstrate that this binding is sensitive to heat, to proteinase K and to pronase treatments. Finally, we show in vitro that the interaction of NK cells with F. nucleatum leads to an NCR1-dependent secretion of TNF-α. Thus, the present study provides the first evidence that NCR1 and NKp46 directly recognize a periodontal pathogen and that this interaction influences the outcome of F. nucleatum-mediated periodontitis

NK cells and cancer: you can teach innate cells new tricks

Natural killer (NK) cells are the prototype innate lymphoid cells endowed with potent cytolytic function that provide host defence against microbial infection and tumours. Here, we review evidence for the role of NK cells in immune surveillance against cancer and highlight new therapeutic approaches for targeting NK cells in the treatment of cancer

Quadriceps femoris muscle fatigue in patients with knee osteoarthritis

M Elboim-Gabyzon,1 N Rozen,2 Y Laufer11Physical Therapy Department, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel; 2Emek Medical Center, Afula, IsraelAbstract: The purpose of this study was to characterize quadriceps femoris muscle fatigue of both lower extremities in patients with knee osteoarthritis (OA). Sixty-two subjects (mean age 68.2 years, standard deviation [SD] ± 7.9 years) with knee OA participated in the study. Significantly higher knee pain was reported in the involved knee than in the contralateral knee, as determined by a visual analog scale. Significant differences were demonstrated between the lower extremities in terms of maximal voluntary isometric contraction, in favor of the less involved leg (P = 0.0001). In contrast, the degree of fatigue of the quadriceps femoris muscle, as measured by the decrement in force production following ten repeated contractions, was significantly higher in the contralateral leg (P = 0.0002). Furthermore, normalization of the fatigue results to the first contraction yielded a similar result (P < 0.0001). Similar results were noted when analysis was performed separately for subjects whose involvement was unilateral or bilateral. The results indicate that, irrespective of the initial strength of contraction, the rate of muscle fatigue in the contralateral leg is significantly higher than in the involved leg. Hypotheses for these unexpected results are suggested. Rehabilitation of patients with knee OA should focus on increasing quadriceps muscle strength and endurance for both lower extremities.Keywords: knee, osteoarthritis, fatigue, quadriceps femoris muscl

The effects of exercise and neuromuscular electrical stimulation in subjects with knee osteoarthritis: a 3-month follow-up study

Yocheved Laufer,1 Haim Shtraker,2 Michal Elboim Gabyzon1 1Physical Therapy Department, Faculty of Social Welfare and Health Sciences, University of Haifa, Israel; 2Department Orthopaedics A and Pediatric Orthopaedics, Western Galilee Medical Center, Nahariya, Israel Background: Strengthening exercises of the quadriceps femoris muscle (QFM) are beneficial for patients with knee osteoarthritis (OA). Studies reporting short-term effects of neuromuscular electrical stimulation (NMES) of the QFM in this population support the use of this modality as an adjunct treatment. The objectives of this follow-up study are to compare the effects of an exercise program with and without NMES of the QFM on pain, functional performance, and muscle strength immediately posttreatment and 12 weeks after completion of the intervention.Methods: Sixty-three participants with knee OA were randomly assigned into two groups receiving 12 biweekly treatments: An exercise-only program or an exercise program combined with NMES.Results: A significantly greater reduction in knee pain was observed immediately after treatment in the NMES group, which was maintained 12 weeks postintervention in both groups. Although at this stage NMES had no additive effect, both groups demonstrated an immediate increase in muscle strength and in functional abilities, with no differences between groups. Although the improvements in gait velocity and in self-report functional ability were maintained at the follow-up session, the noted improvements in muscle strength, time to up and go, and stair negotiation were not maintained. Conclusion: Supplementing an exercise program with NMES to the QFM increased pain modulation immediately after treatment in patients with knee OA. Maintenance of the positive posttreatment effects during a 12-week period was observed only for pain, self-reported functional ability, and walk velocity, with no difference between groups. Clinical rehabilitation effect: The effects of a comprehensive group exercise program with or without NMES are partially maintained 12 weeks after completion of the intervention. The addition of NMES is recommended primarily for its immediate effect on pain. Further studies are necessary to determine the effects of repeated bouts of exercise with and without NMES in this population. Keywords: osteoarthritis, neuromuscular electrical stimulation, exercise, follow-u