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Journal of Immunology (Baltimore, Md. :... Dec 2019The pharyngeal organ is located at the crossroad of the respiratory and digestive tracts in vertebrate, and it is continuously challenged by varying Ags during breathing...
The pharyngeal organ is located at the crossroad of the respiratory and digestive tracts in vertebrate, and it is continuously challenged by varying Ags during breathing and feeding. In mammals, the pharyngeal mucosa (PM) is a critical first line of defense. However, the evolutionary origins and ancient roles of immune defense and microbiota homeostasis of PM are still unknown. In this study, to our knowledge, we are the first to find that diffuse MALT is present in PM of rainbow trout, an early vertebrate. Importantly, following parasitic infection, we detect that strong parasite-specific mucosal IgT and dominant proliferation of IgT B cell immune responses occurs in trout PM, providing, to our knowledge, the first demonstration of local mucosal Ig responses against pathogens in pharyngeal organ of a nonmammal species. Moreover, we show that the trout PM microbiota is prevalently coated with secretory IgT and, to a much lesser degree, by IgM and IgD, suggesting the key role of mucosal Igs in the immune exclusion of teleost pharyngeal bacteria. Overall, to our knowledge, our findings provide the first evidence that pharyngeal mucosal immunity appear earlier than tetrapods.
Topics: Animals; Biological Evolution; Homeostasis; Oncorhynchus mykiss; Pharyngitis; Respiratory Mucosa
PubMed: 31645417
DOI: 10.4049/jimmunol.1900863 -
Clinical Microbiology and Infection :... Dec 2009Screening patients for methicillin-resistant Staphylococcus aureus (MRSA) carriage at hospital admission is widely accepted as an essential part of MRSA control... (Review)
Review
Screening patients for methicillin-resistant Staphylococcus aureus (MRSA) carriage at hospital admission is widely accepted as an essential part of MRSA control programmes. It is assumed, although not proven, that rapid reporting of screening results will improve MRSA control, provided that a clear action plan for positive cases is in place and is being followed. An effective culture screening method is direct inoculation of pooled nose, throat and perineal swabs on a well-performing MRSA-selective chromogenic agar; presumptive MRSA colonies can be confirmed rapidly by latex agglutination with antibodies directed against penicillin-binding protein 2a. This method will usually produce a positive result after 24 h of incubation in >95% of true-positive cases, and will be sufficient for most initial treatment and infection control decisions; full antimicrobial susceptibilities will be available on the next day. Inoculation of selective enrichment broth containing a colorimetric growth indicator is an alternative overnight culture method, but there may be problems with overgrowth of other organisms, such as enterococci. PCR methods are now available that can produce same-day results, provided that samples reach the laboratory in time for batch processing, but cultures are required for susceptibility testing. In comparison with culture-based methods, PCR tests are costly, and some have relatively high false-positivity rates; definitive evidence of their clinical cost-effectiveness is lacking. New point-of-care PCR tests are being introduced that are potentially even more rapid but are even more expensive; studies on the clinical cost-effectiveness of these very rapid tests are awaited.
Topics: Bacteriological Techniques; Carrier State; Cross Infection; Diagnostic Tests, Routine; Humans; Mass Screening; Methicillin-Resistant Staphylococcus aureus; Nasal Mucosa; Perineum; Pharynx; Polymerase Chain Reaction; Staphylococcal Infections
PubMed: 19951329
DOI: 10.1111/j.1469-0691.2009.03092.x -
MBio Aug 2021Oropharyngeal candidiasis (OPC) is the most prevalent oral infection in immunocompromised patients, primarily associated with Candida albicans. Increasing evidence...
Oropharyngeal candidiasis (OPC) is the most prevalent oral infection in immunocompromised patients, primarily associated with Candida albicans. Increasing evidence points to a significant role of mucosal bacteria on the transition of C. albicans from commensal to pathogenic. In this work, we hypothesized that changes in the abundance or composition of the mucosal bacterial microbiota induced by dietary sucrose during the development of OPC can modulate C. albicans virulence. C. albicans burdens and mucosal lesions were evaluated in a mouse cortisone immunosuppression model amended with sucrose. We also analyzed the mucosal bacterial composition using 16S rRNA gene sequencing and culture methods. In immunocompetent mice, sucrose significantly increased total bacterial burdens and reduced alpha diversity, by increasing the relative abundance of mitis group streptococci. In immunocompromised mice, C. albicans infection was associated with a significantly reduced bacterial alpha diversity due to an increase in the relative abundance of enterococci. When exposed to dietary sucrose, these mice had reduced C. albicans burdens and reduced bacterial alpha diversity, associated with an increase in the relative abundance of . SparCC correlation networks showed a significant negative correlation between and in all -infected mice. Depletion of lactobacilli with antibiotic treatment partially restored C. albicans burdens in mice receiving sucrose. In coculture experiments, mouse oral Lactobacillus johnsonii isolates inhibited growth of Enterococcus faecalis isolates and C. albicans. These results support the hypothesis that the sucrose-induced attenuation of C. albicans virulence was a result of changes in the mucosal bacterial microbiome characterized by a reduction in enterococci and an increase in lactobacilli. By comparing Candida albicans virulence and the mucosal bacterial composition in a mouse oral infection model, we were able to dissect the effects of the host environment (immunosuppression), infection with C. albicans, and local modulating factors (availability of sucrose as a carbon source) on the mucosal bacterial microbiome and its role on fungal virulence. We showed that changes in endogenous microbial communities in response to sucrose can lead to attenuation of fungal disease. We also showed that Lactobacillus johnsonii may curtail virulence both by inhibiting its growth and by inhibiting the growth of potentially synergistic bacteria such as enterococci. Our results support the concept that pathogenesis should be viewed in the contexts of both a susceptible host and a mucosal bacterial microbiota conducive to virulence.
Topics: Animals; Candida albicans; Candidiasis, Oral; Disease Models, Animal; Female; Lactobacillus; Mice; Mice, Inbred C57BL; Microbial Interactions; Microbiota; Mouth Mucosa; Oropharynx; RNA, Ribosomal, 16S; Sucrose; Virulence
PubMed: 34399623
DOI: 10.1128/mBio.01937-21 -
BMC Cancer Nov 2011Human papillomaviruses (HPV) are causally associated with ano-genital and a subset of head and neck cancers. Rising incidence of HPV+ anal cancers and head and neck...
BACKGROUND
Human papillomaviruses (HPV) are causally associated with ano-genital and a subset of head and neck cancers. Rising incidence of HPV+ anal cancers and head and neck cancers have now been demonstrated in the developed world over the last decade. The majority of published data on HPV prevalence at the anal and oro-pharyngeal sites are from studies of higher-risk populations. There is a paucity of data on the prevalence of HPV at non-cervical sites in lower risk, non-HIV+ women and this study was designed to provide initial pilot data on a population of women recalled for colposcopy as part of the UK cervical screening programme.
METHODS
100 non-HIV+ women with abnormal cervical cytology, attending clinic for colposcopic examination were recruited. Swabs from the oro-pharyngeal, anal and cervical sites were taken and DNA extracted. HPV detection and genotyping were performed using a standardised, commercially available PCR-line blot assay, which is used to genotype 37 HPV subtypes known to infect the ano-genital and oro-pharyngeal areas. Strict sampling and laboratory precautions were taken to prevent cross-contamination.
RESULTS
There was a very high prevalence of HPV infection at all three sites: 96.0%, 91.4% and 92.4% at the cervix, anus and oro-pharynx, respectively. Multiple HPV subtype infections were dominant at all 3 mucosal sites. At least one or more HR genotype was present at both the cervix/anus in 39/52 (75.0%) patients; both the cervix/oro-pharynx in 48/56 (85.7%) patients; and both the anus/oro-pharynx in 39/52 (75.0%) patients. HPV 16 infection was highly dominant across all mucosal sites, with over a 2-fold increase over the next most prevalent subtype (HPV 31).
CONCLUSIONS
Women with abnormal smears have widespread infection with high-risk HPV at the cervical, anal and oro-pharyngeal mucosal sites and may represent a higher risk population for HPV disease in the future.
Topics: Adult; Anal Canal; Cervix Uteri; Cross-Sectional Studies; Female; Humans; Middle Aged; Oropharynx; Papillomaviridae; Papillomavirus Infections; Pilot Projects; Polymerase Chain Reaction; United Kingdom; Young Adult
PubMed: 22047498
DOI: 10.1186/1471-2407-11-473 -
Emerging Infectious Diseases Jan 2021Analyses of infection chains have demonstrated that severe acute respiratory syndrome coronavirus 2 is highly transmissive. However, data on postmortem stability and...
Analyses of infection chains have demonstrated that severe acute respiratory syndrome coronavirus 2 is highly transmissive. However, data on postmortem stability and infectivity are lacking. Our finding of nasopharyngeal viral RNA stability in 79 corpses showed no time-dependent decrease. Maintained infectivity is supported by virus isolation up to 35 hours postmortem.
Topics: COVID-19; Cadaver; Humans; Nasopharynx; RNA, Viral; Respiratory Mucosa; SARS-CoV-2
PubMed: 33327991
DOI: 10.3201/eid2701.203112 -
Scientific Reports Jan 2020Mucosal melanomas are primary malignant neoplasias originated from melanocytes within mucous membranes in any part of mucosal surface lining, more commonly, in the nasal...
Mucosal melanomas are primary malignant neoplasias originated from melanocytes within mucous membranes in any part of mucosal surface lining, more commonly, in the nasal cavity and accessory sinuses, oral cavity, lips, pharynx, vulvar, vaginal, cervix and anorectal mucosa. Epidemiology data regarding mucosal melanomas in Brazil is scarce, hence the motivation to conduct this research paper. The χ2 test was used to compare categorical variables. Forward stepwise logistic regression method was used in the multivariate analysis to identify independent predictors of early death. A total of 801 patients were included in the analysis. Surgical resection is frequently the first approach to primary tumours (65.3%), even though the utility of lymph node surgery and radiation therapy is not well established. Advanced stage was observed in more than two thirds of patients. Early death was observed in 28.3%. MM cases with regional or distant metastases as well as those located in unusual locations had almost 4 times more risk for early death. Besides that, MM located in lips, oral cavity and pharynx and those receiving chemotherapy had 2 times more risk of early death.
Topics: Brazil; Female; Humans; Logistic Models; Male; Melanoma; Mucous Membrane; Neoplasm Metastasis; Neoplasm Staging; Survival Analysis
PubMed: 31949210
DOI: 10.1038/s41598-019-57253-6 -
JAMA Otolaryngology-- Head & Neck... Aug 2017Pharyngocutaneous fistula formation is an unfortunate complication after salvage laryngectomy for head and neck cancer that is difficult to anticipate and related to a...
IMPORTANCE
Pharyngocutaneous fistula formation is an unfortunate complication after salvage laryngectomy for head and neck cancer that is difficult to anticipate and related to a variety of factors, including the viability of native pharyngeal mucosa.
OBJECTIVE
To examine whether noninvasive angiography with indocyanine green (ICG) dye can be used to evaluate native pharyngeal vascularity to anticipate pharyngocutaneous fistula development.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study included 37 patients enrolled from June 1, 2013, to June 1, 2016, and follow-up was for at least 1 month postoperatively. The study was performed at the University of Alabama at Birmingham, a tertiary care center. Included patients were those undergoing salvage total laryngectomy who were previously treated with chemoradiotherapy or radiotherapy alone.
EXPOSURES
The ICG dye was injected intraoperatively, and laser-assisted vascular imaging was used to evaluate the native pharyngeal mucosa after the ablative procedure. The center of the native pharyngeal mucosa was used as the reference to compare with the peripheral mucosa, and the lowest mean ICG dye percentage of mucosal perfusion was recorded for each patient.
MAIN OUTCOMES AND MEASURES
The primary outcome was the formation of a postoperative fistula, which was assessed by clinical and radiographic assessment to test the hypothesis formulated before data collection.
RESULTS
A total of 37 patients were included (mean [SD] age, 62.3 [8.5] years; 32 [87%] male and 5 [14%] female); 20 had a history of chemoradiotherapy, and 17 had history of radiotherapy alone. Thirty-four patients (92%) had free flap reconstruction, and 3 had primary closure (8%). Ten patients (27%) developed a postoperative fistula. No significant difference was found in fistula rate between patients who underwent neck dissection and those who did not and patients previously treated with chemoradiotherapy and those treated with radiotherapy alone. A receiver operator characteristic curve was generated to determine the diagnostic performance of the lowest mean ICG dye percentage of mucosal perfusion determined by fluorescence imaging, which was found to be a threshold value of 26%. The area under the curve was 0.85 (95% CI, 0.73-0.97), which was significantly greater than the chance diagonal. The overall mean lowest ICG dye percentage of mucosal perfusion was 31.3%. The mean lowest ICG dye percentage of mucosal perfusion was 22.0% in the fistula group vs 34.9% in the nonfistula group (absolute difference, 12.9%; 95% CI, 5.1%-21.7%).
CONCLUSIONS AND RELEVANCE
Patients who developed postoperative fistulas had lower mucosal perfusion as detected by ICG dye angiography when compared with patients who did not develop fistulas.
Topics: Alabama; Angiography; Cutaneous Fistula; Female; Head and Neck Neoplasms; Humans; Indocyanine Green; Laryngectomy; Lasers; Male; Middle Aged; Pharyngeal Diseases; Pharynx; Postoperative Complications; Salvage Therapy
PubMed: 28520896
DOI: 10.1001/jamaoto.2017.0187 -
Frontiers in Cellular and Infection... 2021In humans, nasopharyngeal carriage of is common and although primarily asymptomatic, is a pre-requisite for pneumonia and invasive pneumococcal disease (IPD). Together,... (Review)
Review
In humans, nasopharyngeal carriage of is common and although primarily asymptomatic, is a pre-requisite for pneumonia and invasive pneumococcal disease (IPD). Together, these kill over 500,000 people over the age of 70 years worldwide every year. Pneumococcal conjugate vaccines have been largely successful in reducing IPD in young children and have had considerable indirect impact in protection of older people in industrialized country settings (herd immunity). However, serotype replacement continues to threaten vulnerable populations, particularly older people in whom direct vaccine efficacy is reduced. The early control of pneumococcal colonization at the mucosal surface is mediated through a complex array of epithelial and innate immune cell interactions. Older people often display a state of chronic inflammation, which is associated with an increased mortality risk and has been termed 'Inflammageing'. In this review, we discuss the contribution of an altered microbiome, the impact of inflammageing on human epithelial and innate immunity to , and how the resulting dysregulation may affect the outcome of pneumococcal infection in older individuals. We describe the impact of the pneumococcal vaccine and highlight potential research approaches which may improve our understanding of respiratory mucosal immunity during pneumococcal colonization in older individuals.
Topics: Aged; Child; Child, Preschool; Humans; Immunity, Innate; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 34113578
DOI: 10.3389/fcimb.2021.651474 -
Microbial Biotechnology Jan 2023Respiratory viruses such as influenza viruses, respiratory syncytial virus (RSV), and coronaviruses initiate infection at the mucosal surfaces of the upper respiratory...
Respiratory viruses such as influenza viruses, respiratory syncytial virus (RSV), and coronaviruses initiate infection at the mucosal surfaces of the upper respiratory tract (URT), where the resident respiratory microbiome has an important gatekeeper function. In contrast to gut-targeting administration of beneficial bacteria against respiratory viral disease, topical URT administration of probiotics is currently underexplored, especially for the prevention and/or treatment of viral infections. Here, we report the formulation of a throat spray with live lactobacilli exhibiting several in vitro mechanisms of action against respiratory viral infections, including induction of interferon regulatory pathways and direct inhibition of respiratory viruses. Rational selection of Lactobacillaceae strains was based on previously documented beneficial properties, up-scaling and industrial production characteristics, clinical safety parameters, and potential antiviral and immunostimulatory efficacy in the URT demonstrated in this study. Using a three-step selection strategy, three strains were selected and further tested in vitro antiviral assays and in formulations: Lacticaseibacillus casei AMBR2 as a promising endogenous candidate URT probiotic with previously reported barrier-enhancing and anti-pathogenic properties and the two well-studied model strains Lacticaseibacillus rhamnosus GG and Lactiplantibacillus plantarum WCFS1 that display immunomodulatory capacities. The three strains and their combination significantly reduced the cytopathogenic effects of RSV, influenza A/H1N1 and B viruses, and HCoV-229E coronavirus in co-culture models with bacteria, virus, and host cells. Subsequently, these strains were formulated in a throat spray and human monocytes were employed to confirm the formulation process did not reduce the interferon regulatory pathway-inducing capacity. Administration of the throat spray in healthy volunteers revealed that the lactobacilli were capable of temporary colonization of the throat in a metabolically active form. Thus, the developed spray with live lactobacilli will be further explored in the clinic as a potential broad-acting live biotherapeutic strategy against respiratory viral diseases.
Topics: Humans; Lactobacillus; Pharynx; Influenza A Virus, H1N1 Subtype; Influenza, Human; Respiratory Syncytial Viruses; Virus Diseases; Antiviral Agents; Coronavirus Infections; Interferons
PubMed: 36468246
DOI: 10.1111/1751-7915.14189 -
BMC Cancer Sep 2021The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that informs clinical decisions regarding recurrence and overall survival in most...
BACKGROUND
The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that informs clinical decisions regarding recurrence and overall survival in most epithelial cancers. Radiotherapy for head and neck cancer leads to mucositis in almost all patients and severe radiation-mucositis affects their quality of life (QOL). However, little is known about the NLR for severe mucositis. Therefore, this study aimed to show the association between the NLR and severe radiation-induced mucositis in hypopharyngeal or laryngeal cancer patients.
METHODS
In this retrospective study, we determined the incidence of grade 3 mucositis in 99 patients who were receiving definitive radiotherapy or chemoradiotherapy (CRT) for hypopharyngeal or laryngeal cancer. We performed univariate and multivariate logistic regression analyses to investigate the characteristics of grade 3 mucositis. Kaplan-Meier curves and log-rank tests were used to evaluate the occurrence of grade 3 mucositis between two groups with high (NLR > 5) or low (NLR < 5) systemic inflammation.
RESULTS
The incidence of grade 3 mucositis was 39%. Univariate logistic regression analysis showed that the NLR (Odd ratio [OR] = 1.09; 95% confidence interval [CI] = 1.02-1.16; p = 0.016) and smoking (OR = 1.02; 95% CI = 1.00-1.03; p = 0.048) were significantly associated with grade 3 mucositis. Multivariate logistic regression analysis showed that the NLR was independently associated with grade 3 mucositis (OR = 1.09; 95% CI = 1.01-1.17; p = 0.021). Kaplan-Meier curves also showed that patients with higher NLR (NLR > 5) prior to radiotherapy developed grade 3 mucositis more frequently than those with lower NLR during radiotherapy (p = 0.045).
CONCLUSION
This study suggests that a higher NLR is a risk factor and predictor of severe radiation-induced mucositis in hypopharyngeal or laryngeal cancer patients.
Topics: Adult; Aged; Female; Humans; Hypopharyngeal Neoplasms; Kaplan-Meier Estimate; Laryngeal Diseases; Laryngeal Neoplasms; Leukocyte Count; Logistic Models; Lymphocyte Count; Lymphocytes; Male; Middle Aged; Mucositis; Neutrophils; Pharyngeal Diseases; Quality of Life; Radiation Injuries; Retrospective Studies; Smoking
PubMed: 34583669
DOI: 10.1186/s12885-021-08793-6