New Concepts in Immunity to Neisseria Gonorrhoeae: Innate Responses and Suppression of Adaptive Immunity Favor the Pathogen, Not the Host

It is well-known that gonorrhea can be acquired repeatedly with no apparent development of protective immunity arising from previous episodes of infection. Symptomatic infection is characterized by a purulent exudate, but the host response mechanisms are poorly understood. While the remarkable antigenic variability displayed by Neisseria gonorrhoeae and its capacity to inhibit complement activation allow it to evade destruction by the host's immune defenses, we propose that it also has the capacity to avoid inducing specific immune responses. In a mouse model of vaginal gonococcal infection, N. gonorrhoeae elicits Th17-driven inflammatory–immune responses, which recruit innate defense mechanisms including an influx of neutrophils. Concomitantly, N. gonorrhoeae suppresses Th1- and Th2-dependent adaptive immunity, including specific antibody responses, through a mechanism involving TGF-β and regulatory T cells. Blockade of TGF-β alleviates the suppression of specific anti-gonococcal responses and allows Th1 and Th2 responses to emerge with the generation of immune memory and protective immunity. Genital tract tissues are naturally rich in TGF-β, which fosters an immunosuppressive environment that is important in reproduction. In exploiting this niche, N. gonorrhoeae exemplifies a well-adapted pathogen that proactively elicits from its host innate responses that it can survive and concomitantly suppresses adaptive immunity. Comprehension of these mechanisms of gonococcal pathogenesis should allow the development of novel approaches to therapy and facilitate the development of an effective vaccine

In-vitro-Studie zur Oberflächenqualität eines Versieglers nach chemischer Belastung

Dentale Kunststoffversiegler werden eingesetzt um die Entwicklung kariogener Biofilme in Fissuren und Grübchen der Zahnoberflächen zu unterbinden. Die Alterungsprozesse zahnmedizinischer Kunststoffe in der Mundhöhle sind bisher nicht umfassend untersucht. Alterung kann durch physikalische und chemische Degradation erfolgen. Mit steigendem Konsum industriell verarbeiteter, weicher, zucker- und säurehaltiger Nahrung gewinnen nicht nur Erosions-, sondern auch Korrosionsprozesse an allen oral exponierten natürlichen und artifiziellen Oberflächen an Bedeutung. Dentale Kunststoff-Degradation kann ebenfalls von intraoral vorkommenden Enzymen verursacht werden. Außerdem besitzen zahlreiche Mundhygieneartikel einen kritischen pH-Wert von < 5,5 und weisen somit erosives und korrosives Potential speziell für die Zahnhartsubstanzen auf. Die Merkmale chemischer Degradation von kunststoffbasierten Fissurenversieglern können eine Zunahme der Rauheit sowie die Erweichung der Oberfläche sein. Die chemische Widerstandsfähigkeit aktuell gebräuchlicher zahnärztlicher Materialien gegenüber alltäglich möglichen korrosiven Effekten ist häufig nicht bekannt. Intraoral sind die Wechselwirkungen von Alterung und Verschleiß aufgrund einer Vielzahl weiterer Umgebungseinflüsse äußerst komplex. Deshalb war es das Ziel der vorliegenden experimentellen Studie, die chemische Beeinflussung der Oberflächenqualität eines Kunststoffversieglers (Helioseal) in vitro zu untersuchen. Als Prüfagenzien wurden Zitronensäure (1%), alkoholhaltiges sowie ätherische Öle beinhaltendes Mundhygienespray (theranovis oral), eine ätherische Öle enthaltende, ethanolfreie Mundspülung (Listerine Zero) und das Enzym Pseudocholinesterase (PCE) eingesetzt. Tafelwasser diente der Kontrolle. Für die Versuchsreihen wurden kariesfreie menschliche Molaren (n = 78) verwendet, die vom Zeitpunkt der Extraktion beginnend in 0,1%iger Thymollösung gelagert wurden. Nach Rehydrierung, Abtrennen der Wurzeln, Reinigung und Schmelz-Ätzung wurden in vitro Fissurenversiegelungen erstellt. Zur Anfertigung interner Kontrollen erfolgte die halbseitige Abdeckung mit Silikon. Zur Simulation der chemischen Belastung wurden versiegelte Molaren über 2 Wochen für 3-mal 1 min oder 1 h täglich oder dauerhaft bei Raumtemperatur in die Prüfagenzien Zitronensäure, Mundspray und Mundspülung eingelegt. Die Belastung mit PCELösung und Tafelwasser erfolgte bei 37° C im Inkubator über 2 und 4 Wochen. Ziele waren die Bewertung der Oberflächenqualität sowie die Analyse der Randzonen der Fissurenversiegelungen mittels Licht- und Rasterelektronenmikroskopie. In Vorversuchen wurden die Parameter Politur, Sauerstoffinhibitionsschicht und Lagerungsdauer geprüft. Als weitere Proben dienten Materialplättchen (n = 90). Diese wurden für 14 Tage in die 5 Prüfagenzien eingelegt, um die Oberflächenhärte und die Rauheit zu messen. Nach chemischer Belastung konnten keine visuell erkennbaren Oberflächenveränderungen und keine Zunahme der Oberflächenrauheit des Kunststoff-Fissurenversieglers detektiert werden. Nach Exposition gegenüber 1%iger Zitronensäure zeigten sich bei allen versiegelten Molaren Randstufen und Unterminierungen durch erosiven Verlust des umgrenzenden Zahnschmelzes. Die Mikrohärte der Materialplättchen war insbesondere nach chemischer Belastung mit der Mundspülung signifikant verringert, aber auch nach Belastung durch Zitronensäure und Mundspray gegenüber der in Wasser gelagerten Kontrollproben reduziert (p < 0,05). Aus den Ergebnissen dieser In-vitro-Studie kann geschlussfolgert werden, dass die Haltbarkeit von Fissurenversiegelungen mittels chemischer Degradation durch Mundhygieneprodukte beeinträchtigt werden kann. Saure Nahrungsmittel und Getränke können durch Schmelzerosion zu einer Destabilisierung der Interaktionszone zwischen Zahnschmelz und Fissurenversiegelung führenDental resin-based sealants are used to inhibit the development of cariogenic biofilms in fissures and pits of tooth surfaces. The aging processes of synthetic dental materials in the oral cavity have not yet been comprehensively examined. Ageing can occur through physical and chemical degradation. Due to the growing consumption of commercially processed, soft diet rich in sugar and acids, erosion and corrosion processes of all orally exposed natural and artificial surfaces have become increasingly important issues. Degradation can also be caused by intraorally occurring enzymes. In addition, numerous oral hygiene products have critical pH values of < 5.5 and thereby represent erosive and corrosive potential, particularly for tooth structures. The pattern of chemical degradation of resin-based fissure sealants can include an increase in roughness and softening of the surface. The chemical resistance of dental materials currently in use with regard to everyday possible corrosive effects is mostly not known. Intraoral interdependencies of age and wear due to a variety of other environmental influences are extremely complex. The objective of the present experimental study was therefore to examine the chemical impact of the surface quality of a resin-based sealant (Helioseal) in vitro. The used testing agents were: citric acid (1%), oral hygiene spray containing alcohol and essential oils (theranovis oral), an ethanol-free mouthwash containing essential oils (Listerine Zero) and the enzyme butyrylcholinesterase (BChE). Water was used as control. Human molars without caries (n = 78) were used for the testing series; after extraction, the molars had been stored in a 0.1 percent thymol solution. After rehydration, separation of the roots, cleaning and etching of the enamel, fissure sealant was applied in vitro. Half of the occlusal surface was covered with silicon in order to provide internal controls. To simulate chemical exposure, the sealed molars were submerged in the testing agents citric acid, mouth spray and mouthwash at room temperature three times for one minute each, one hour a day or continously for two weeks. They were exposed to the BChE solution and water in an incubator at 37° C for two and four weeks. The objectives were to evaluate the surface quality and to analyze the marginal zones of the fissure sealant by means of light and scanning electron microscopy. In preliminary tests polish, oxygen inhibition layer and storage periods were tested. Material platelets (n = 90) were used as additional specimens. These were submerged in the five testing agents for 14 days in order to measure the surface hardness and roughness. After chemical exposure, no visually recognizable surface changes and no increase in the surface roughness of the resin-based fissure sealant could be detected. After exposure to the citric acid, all of the sealed molars displayed marginal ridges and undermining caused by erosive loss of the surrounding enamel. The microhardness of the material platelets in particular was significantly reduced after chemical exposure with the mouthwash, as well as after exposure to citric acid and mouth spray compared to control specimens exposed to water (p < 0.05). It can be concluded from the results of this in-vitro-study that the durability of fissure sealants can be compromised by chemical degradation from oral hygiene products. Acidic foods and drinks can lead to a destabilization of the interaction zone between tooth enamel and fissure sealant due to enamel erosion

Haemophilus influenzae Infection Drives IL-17-Mediated Neutrophilic Allergic Airways Disease

A subset of patients with stable asthma has prominent neutrophilic and reduced eosinophilic inflammation, which is associated with attenuated airways hyper-responsiveness (AHR). Haemophilus influenzae has been isolated from the airways of neutrophilic asthmatics; however, the nature of the association between infection and the development of neutrophilic asthma is not understood. Our aim was to investigate the effects of H. influenzae respiratory infection on the development of hallmark features of asthma in a mouse model of allergic airways disease (AAD). BALB/c mice were intraperitoneally sensitized to ovalbumin (OVA) and intranasally challenged with OVA 12–15 days later to induce AAD. Mice were infected with non-typeable H. influenzae during or 10 days after sensitization, and the effects of infection on the development of key features of AAD were assessed on day 16. T-helper 17 cells were enumerated by fluorescent-activated cell sorting and depleted with anti-IL-17 neutralizing antibody. We show that infection in AAD significantly reduced eosinophilic inflammation, OVA-induced IL-5, IL-13 and IFN-γ responses and AHR; however, infection increased airway neutrophil influx in response to OVA challenge. Augmented neutrophilic inflammation correlated with increased IL-17 responses and IL-17 expressing macrophages and neutrophils (early, innate) and T lymphocytes (late, adaptive) in the lung. Significantly, depletion of IL-17 completely abrogated infection-induced neutrophilic inflammation during AAD. In conclusion, H. influenzae infection synergizes with AAD to induce Th17 immune responses that drive the development of neutrophilic and suppress eosinophilic inflammation during AAD. This results in a phenotype that is similar to neutrophilic asthma. Infection-induced neutrophilic inflammation in AAD is mediated by IL-17 responses

Mahomet Aquifer Protection Task Force: Findings and Recommendations

The Mahomet Aquifer is one of Illinois’ most important groundwater resources, serving as the primary source of drinking water for more than 500,000 people in 15 Illinois counties and providing an estimated 220 million gallons of water per day to communities, agriculture, industry, and rural wells. In 2017, the Illinois General Assembly created the Mahomet Aquifer Protection Task Force (Task Force) to identify gaps in existing aquifer-protection regulations and efforts, specifically by: Developing a state plan to maintain the groundwater quality of the Mahomet Aquifer; Identifying current and potential contamination threats to the water quality of the Mahomet Aquifer; Identifying actions that might be taken to ensure the long-term protection of the Mahomet Aquifer; and Making legislative recommendations for the protection of the Mahomet Aquifer. The Task Force investigated and considered various actions, including legislative actions, to ensure the long-term protection of the Mahomet Aquifer and makes the following prioritized recommendations to the General Assembly and the Governor: 1. Provide 19.8 million dollars to the Prairie Research Institute (PRI) to use helicopter-based time-domain electromagnetics (HTEM) technology to more accurately map and characterize the Mahomet Aquifer to aid in identifying the connections with other aquifers and surface waters. 2. Use HTEM and other techniques to identify areas where the Mahomet Aquifer is recharged. 3. Integrate data collected via HTEM into next-generation groundwater flow models. 4. Develop and implement source water protection plans pursuant to 35 Ill. Adm. Code 604 Subpart C, after the effective date of adoption, for the community water supplies determined to be susceptible to groundwater contamination. 5. Implement the recommendations outlined for each identified threat and potential threat (as detailed below and in Section III.A) and provide additional funding (1 million dollars for one-time equipment acquisition and an additional 2.3 million annually) to PRI to deploy state-of-the-art monitoring networks and create the analytical capability to identify emerging contaminants of concern. 6. Improve education and outreach regarding the Mahomet Aquifer such that all stakeholders are better informed about water resources, water demand, and water supply planning and management, particularly when plans are made, reviewed, and updated. 7. Develop a group with a mission similar to the Mahomet Aquifer Protection Task Force that is a blend of other select individuals that serve in a quasi-government or government capacity to provide leadership, administrative stature, or process for regional water supply. 8. Plan cooperative research and data collection, analysis, management, and exchange by academic institutions, units of government, the private sector, and other stakeholders. 9. Use the established water supply planning process to review and update regional and local water supply plans at least every five years. 10. Ensure comprehensive use reporting by consistently and fully funding the Illinois Water Inventory Program.Illinois General AssemblyOpe