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Water Filtered Infrared A and Visible Light (wIRA/VIS) Irradiation Reduces Chlamydia trachomatis Infectivity Independent of Targeted Cytokine Inhibition.

ABSTRACT: Chlamydia trachomatis is the major cause of infectious blindness and represents the most common bacterial sexually transmitted infection worldwide. Considering the potential side effects of antibiotic therapy and increasing threat of antibiotic resistance, alternative therapeutic strategies are needed. Previous studies showed that water filtered infrared A alone (wIRA) or in combination with visible light (wIRA/VIS) reduced C. trachomatis infectivity. Furthermore, wIRA/VIS irradiation led to secretion of pro-inflammatory cytokines similar to that observed upon C. trachomatis infection. We confirmed the results of previous studies, namely that cytokine secretion (IL-6, IL-8, and RANTES/CCL5) upon wIRA/VIS treatment, and the subsequent reduction of chlamydial infectivity, are independent of the addition of cycloheximide, a host protein synthesis inhibitor. Reproducible cytokine release upon irradiation indicated that cytokines might be involved in the anti-chlamydial mechanism of wIRA/VIS. This hypothesis was tested by inhibiting IL-6, IL-8, and RANTES secretion in C. trachomatis or mock-infected cells by gene silencing or pharmaceutical inhibition. Celastrol, a substance derived from Trypterygium wilfordii, used in traditional Chinese medicine and known for anti-cancer and anti-inflammatory effects, was used for IL-6 and IL-8 inhibition, while Maraviroc, a competitive CCR5 antagonist and anti-HIV drug, served as a RANTES/CCL5 inhibitor. HeLa cell cytotoxicity and impact on chlamydial morphology, size and inclusion number was evaluated upon increasing inhibitor concentration, and concentrations of 0.1 and 1 ?M Celastrol and 10 and 20 ?M Maraviroc were subsequently selected for irradiation experiments. Celastrol at any concentration reduced chlamydial infectivity, an effect only observed for 20 ?M Maraviroc. Triple dose irradiation (24, 36, 40 hpi) significantly reduced chlamydial infectivity regardless of IL-6, IL-8, or RANTES/CCL5 gene silencing, Celastrol or Maraviroc treatment. Neither gene silencing nor pharmaceutical cytokine inhibition provoked the chlamydial stress response. The anti-chlamydial effect of wIRA/VIS is independent of cytokine inhibition under all conditions evaluated. Thus, factors other than host cell cytokines must be involved in the working mechanism of wIRA/VIS. This study gives a first insight into the working mechanism of wIRA/VIS in relation to an integral component of the host immune system and supports the potential of wIRA/VIS as a promising new tool for treatment in trachoma.

SUBMITTER: Kuratli J

PROVIDER: S-EPMC6262300 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Water Filtered Infrared A and Visible Light (wIRA/VIS) Irradiation Reduces Chlamydia trachomatis Infectivity Independent of Targeted Cytokine Inhibition.

Kuratli Jasmin J Pesch Theresa T Marti Hanna H Leonard Cory Ann CA Blenn Christian C Torgerson Paul P Borel Nicole N

Frontiers in microbiology 20181115

Chlamydia trachomatis is the major cause of infectious blindness and represents the most common bacterial sexually transmitted infection worldwide. Considering the potential side effects of antibiotic therapy and increasing threat of antibiotic resistance, alternative therapeutic strategies are needed. Previous studies showed that water filtered infrared A alone (wIRA) or in combination with visible light (wIRA/VIS) reduced C. trachomatis infectivity. Furthermore, wIRA/VIS irradiat ...[more]

PMID: 30524392

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Project description:Due to increasing antibiotic resistance, the application of antimicrobial photodynamic therapy (aPDT) is gaining increasing popularity in dentistry. The aim of this study was to investigate the antimicrobial effects of aPDT using visible light (VIS) and water-filtered infrared-A (wIRA) in combination with a Hypericum perforatum extract on in situ oral biofilms. The chemical composition of H. perforatum extract was analyzed using ultra-high-performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-HRMS). To obtain initial and mature oral biofilms in situ, intraoral devices with fixed bovine enamel slabs (BES) were carried by six healthy volunteers for two hours and three days, respectively. The ex situ exposure of biofilms to VIS?+?wIRA (200 mWcm-2) and H. perforatum (32?mg?ml-1, non-rinsed or rinsed prior to aPDT after 2-min preincubation) lasted for five minutes. Biofilm treatment with 0.2% chlorhexidine gluconate solution (CHX) served as a positive control, while untreated biofilms served as a negative control. The colony-forming units (CFU) of the aPDT-treated biofilms were quantified, and the surviving microorganisms were identified using MALDI-TOF biochemical tests as well as 16?S rDNA-sequencing. We could show that the H. perforatum extract had significant photoactivation potential at a concentration of 32?mg?ml-1. When aPDT was carried out in the presence of H. perforatum, all biofilms (100%) were completely eradicated (p?=?0.0001). When H. perforatum was rinsed off prior to aPDT, more than 92% of the initial viable bacterial count and 13% of the mature oral biofilm were killed. Overall, the microbial composition in initial and mature biofilms was substantially altered after aPDT, inducing a shift in the synthesis of the microbial community. In conclusion, H. perforatum-mediated aPDT using VIS?+?wIRA interferes with oral biofilms, resulting in their elimination or the substantial alteration of microbial diversity and richness. The present results support the evaluation of H. perforatum-mediated aPDT for the adjunctive treatment of biofilm-associated oral diseases.

Project description:New therapeutic strategies are needed to overcome drawbacks in treatment of infections with intracellular bacteria. Chlamydiaceae are Gram-negative bacteria implicated in acute and chronic diseases such as abortion in animals and trachoma in humans. Water-filtered infrared A (wIRA) is short wavelength infrared radiation with a spectrum ranging from 780 to 1400 nm. In clinical settings, wIRA alone and in combination with visible light (VIS) has proven its efficacy in acute and chronic wound healing processes. This is the first study to demonstrate that wIRA irradiation combined with VIS (wIRA/VIS) diminishes recovery of infectious elementary bodies (EBs) of both intra- and extracellular Chlamydia (C.) in two different cell lines (Vero, HeLa) regardless of the chlamydial strain (C. pecorum, C. trachomatis serovar E) as shown by indirect immunofluorescence and titration by subpassage. Moreover, a single exposure to wIRA/VIS at 40 hours post infection (hpi) led to a significant reduction of C. pecorum inclusion frequency in Vero cells and C. trachomatis in HeLa cells, respectively. A triple dose of irradiation (24, 36, 40 hpi) during the course of C. trachomatis infection further reduced chlamydial inclusion frequency in HeLa cells without inducing the chlamydial persistence/stress response, as ascertained by electron microscopy. Irradiation of host cells (HeLa, Vero) neither affected cell viability nor induced any molecular markers of cytotoxicity as investigated by Alamar blue assay and Western blot analysis. Chlamydial infection, irradiation, and the combination of both showed a similar release pattern of a subset of pro-inflammatory cytokines (MIF/GIF, Serpin E1, RANTES, IL-6, IL-8) and chemokines (IL-16, IP-10, ENA-78, MIG, MIP-1α/β) from host cells. Initial investigation into the mechanism indicated possible thermal effects on Chlamydia due to irradiation. In summary, we demonstrate a non-chemical reduction of chlamydial infection using the combination of water-filtered infrared A and visible light.

Project description:Case description: A patient with a Barrett oesophageal carcinoma and a resection of the oesophagus with gastric pull-up developed swallowing disorders 6 years and 2 months after the operation. Within 1 year and 7 months two recurrences of the tumor at the anastomosis were found and treated with combined chemoradiotherapy or chemotherapy respectively. 7 years and 9 months after the operation local tumor masses and destruction were present with no ability to orally drink or eat (full feeding by jejunal PEG tube): quality of life was poor, as saliva and mucus were very viscous (pulling filaments) and could not be swallowed and had to be spat out throughout the day and night resulting in short periods of sleep (awaking from the necessity to spit out). In total the situation was interpreted more as a problem related to a feeling of choking (with food or fluid) in the sense of a functional dysphagia rather than as a swallowing disorder from a structural stenosis. At that time acetylcysteine (2 times 200 mg per day, given via the PEG tube) and irradiation with water-filtered infrared-A (wIRA), a special form of heat radiation, of the ventral part of the neck and the thorax were added to the therapy. Within 1 day with acetylcysteine saliva and mucus became less viscous. Within 2 days with wIRA (one day with 4 to 5 hours with irradiation with wIRA at home) salivation decreased markedly and quality of life clearly improved: For the first time the patient slept without interruption and without the need for sleep-inducing medication. After 5 days with wIRA the patient could eat his first soft dumpling although drinking of fluids was still not possible. After 2½ weeks with wIRA the patient could eat his first minced schnitzel (escalope). Following the commencement of wIRA (with typically approximately 90-150 minutes irradiation with wIRA per day) the patient had 8 months with good quality of life with only small amounts of liquid saliva and mucus and without the necessity to spit out. During this period the patient was able to sleep during the night. Discussion: The main physiological effects of water-filtered infrared-A (wIRA) are: wIRA increases tissue temperature, tissue oxygen partial pressure and tissue perfusion markedly. The five main clinical effects of wIRA are: wIRA decreases pain, inflammation and exudation/hypersecretion, and promotes infection defense and regeneration, all in a cross-indication manner. Therefore there is a wide range of indications for wIRA. The effects of wIRA are based on both its thermal effects (relying on transfer of heat energy) and thermic effects (temperature-dependent effects, occurring together with temperature changes) as well as on non-thermal and temperature-independent effects like direct effects on cells, cell structures or cell substances. Conclusion: Besides in a variety of other indications for wIRA, in cases of swallowing disorders (functional dysphagia) and hypersalivation or hypersecretion of mucus the use of wIRA should be considered as part of the treatment regime for improving a patient's quality of life.

Project description:Water-filtered infrared-A (wIRA) is a special form of heat radiation with high tissue penetration and a low thermal load to the skin surface. wIRA corresponds to the major part of the sun's heat radiation, which reaches the surface of the Earth in moderate climatic zones filtered by water and water vapour of the atmosphere. wIRA promotes healing of acute and chronic wounds both by thermal and thermic as well as by non-thermal and non-thermic cellular effects.This publication includes a literature review with search in PubMed/Medline for "water-filtered infrared-A" and "wound"/"ulcus" or "wassergefiltertes Infrarot A" and "Wunde"/"Ulkus", respectively (publications in English and German), and additional analysis of study data. Seven prospective clinical studies (of these six randomized controlled trials (RCT), the largest study with n=400 patients) were identified and included. All randomized controlled clinical trials compare a combination of high standard care plus wIRA treatment vs. high standard care alone. The results below marked with "vs." present these comparisons.wIRA increases tissue temperature (+2.7°C at a tissue depth of 2 cm), tissue oxygen partial pressure (+32% at a tissue depth of 2 cm) and tissue perfusion (effect sizes within the wIRA group). wIRA promotes normal as well as disturbed wound healing by diminishing inflammation and exudation, by promotion of infection defense and regeneration, and by alleviation of pain (with respect to alleviation of pain, without any exception during 230 irradiations, 13.4 vs. 0.0 on a visual analogue scale (VAS 0-100), median difference between groups 13.8, 95% confidence interval (CI) 12.3/16.7, p<0.000001) with a substantially reduced need for analgesics (52-69% less in the three groups with wIRA compared to the three control groups in visceral surgery, p=0.000020 and 0.00037 and 0.0045, respectively; total of 6 vs. 14.5 analgesic tablets on 6 surveyed days (of weeks 1-6) in chronic venous stasis ulcers, median difference -8, 95% CI -10/-5, p=0.000002). Further effects are: Faster reduction of wound area (in severely burned children: 90% reduction of wound size after 9 vs. 13 days, after 9 days 89.2% vs. 49.5% reduction in wound area, median difference 39.5% wound area reduction, 95% CI 36.7%/42.2%, p=0.000011; complete wound closure of chronic venous stasis ulcers after 14 vs. 42 days, median difference -21 days, 95% CI -28/-10, p=0.000005). Better overall evaluation of wound healing (surgical wounds: 88.6 vs. 78.5 on a VAS 0-100, median difference 8.9, 95% CI 6.1/12.0, p<0.000001). Better overall evaluation of the effect of irradiation (79.0 vs. 46.8 on a VAS 0-100 with 50 as neutral point, median difference 27.9, 95% CI 19.8/34.6, p<0.000001). Higher tissue oxygen partial pressure during irradiation with wIRA (at a tissue depth of 2 cm 41.6 vs. 30.2 mmHg, median difference 11.9 mmHg, 95% CI 9.6/14.2 mmHg, p<0.000001). Higher tissue temperature during irradiation with wIRA (at a tissue depth of 2 cm 38.9 vs. 36.4°C, median difference 2.6°C, 95% CI 2.2/2.9°C, p<0.000001). Better cosmetic result (84.5 vs. 76.5 on a VAS 0-100, median difference 7.9, 95% CI 3.7/12.0, p=0.00027). Lower wound infection rate (single preoperative irradiation: 5.1% vs. 12.1% wound infections in total, difference -7.0%, 95% CI -12.8%/-1.3%, p=0.017, of these: late wound infections (postoperative days 9-30) 1.7% vs. 7.7%, difference -6.0%, 95% CI -10.3%/-1.7%, p=0.007). Shorter hospital stay (9 vs. 11 postoperative days, median difference -2 days, 95% CI -3/0 days, p=0.022). Most of the effects have been proven with an evidence level of 1a or 1b.Water-filtered infrared-A is a useful complement for the treatment of acute and chronic wounds.

Project description:Bacteria of the genus Chlamydia include the significant human pathogens Chlamydia trachomatis and C. pneumoniae All chlamydiae are obligate intracellular parasites that depend on infection of a host cell and transition through a biphasic developmental cycle. Following host cell invasion by the infectious elementary body (EB), the pathogen transitions to the replicative but noninfectious reticulate body (RB). Differentiation of the RB back to the EB is essential to generate infectious progeny. While the EB form has historically been regarded as metabolically inert, maintenance of infectivity during incubation with specific nutrients has revealed active maintenance of the infectious phenotype. Using transcriptome sequencing, we show that the transcriptome of extracellular EBs incubated under metabolically stimulating conditions does not cluster with germinating EBs but rather with the transcriptome of EBs isolated directly from infected cells. In addition, the transcriptional profile of the extracellular metabolizing EBs more closely resembled that of EB production than germination. Maintenance of infectivity of extracellular EBs was achieved by metabolizing chemically diverse compounds, including glucose 6-phosphate, ATP, and amino acids, all of which can be found in extracellular environments, including mucosal secretions. We further show that the EB cell type actively maintains infectivity in the inclusion after terminal differentiation. Overall, these findings contribute to the emerging understanding that the EB cell form is actively maintained through metabolic processes after terminal differentiation to facilitate prolonged infectivity within the inclusion and under host cell free conditions, for example, following deposition at mucosal surfaces.IMPORTANCE Chlamydiae are obligate intracellular Gram-negative bacteria that are responsible for a wide range of diseases in both animal and human hosts. According to the Centers for Disease Control and Prevention, C. trachomatis is the most frequently reported sexually transmitted infection in the United States, costing the American health care system nearly $2.4 billion annually. Every year, there are over 4 million new cases of Chlamydia infections in the United States and an estimated 100 million cases worldwide. To cause disease, Chlamydia must successfully complete its complex biphasic developmental cycle, alternating between an infectious cell form (EB) specialized for initiating entry into target cells and a replicative form (RB) specialized for creating and maintaining the intracellular replication niche. The EB cell form has historically been considered metabolically quiescent, a passive entity simply waiting for contact with a host cell to initiate the next round of infection. Recent studies and data presented here demonstrate that the EB maintains its infectious phenotype by actively metabolizing a variety of nutrients. Therefore, the EB appears to have an active role in chlamydial biology, possibly within multiple environments, such as mucosal surfaces, fomites, and inside the host cell after formation.

Dataset Information

Water Filtered Infrared A and Visible Light (wIRA/VIS) Irradiation Reduces Chlamydia trachomatis Infectivity Independent of Targeted Cytokine Inhibition.

Publications

Water Filtered Infrared A and Visible Light (wIRA/VIS) Irradiation Reduces <i>Chlamydia trachomatis</i> Infectivity Independent of Targeted Cytokine Inhibition.

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