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MBio Feb 2016Neisseria meningitidis colonizes the nasopharyngeal mucosa of healthy populations asymptomatically, although the bacterial surface is rich in motifs that activate the...
UNLABELLED
Neisseria meningitidis colonizes the nasopharyngeal mucosa of healthy populations asymptomatically, although the bacterial surface is rich in motifs that activate the host innate immunity. What determines the tolerant host response to this bacterium in asymptomatic carriers is poorly understood. We demonstrated that the conserved meningococcal surface protein NhhA orchestrates monocyte (Mo) differentiation specifically into macrophage-like cells with a CD200R(hi) phenotype (NhhA-Mφ). In response to meningococcal stimulation, NhhA-Mφ failed to produce proinflammatory mediators. Instead, they upregulated interleukin-10 (IL-10) and Th2/regulatory T cell (Treg)-attracting chemokines, such as CCL17, CCL18, and CCL22. Moreover, NhhA-Mφ were highly efficient in eliminating bacteria. The in vivo validity of these findings was corroborated using a murine model challenged with N. meningitidis systematically or intranasally. The NhhA-modulated immune response protected mice from septic shock; Mo/Mφ depletion abolished this protective effect. Intranasal administration of NhhA induced an anti-inflammatory response, which was associated with N. meningitidis persistence at the nasopharynx. In vitro studies demonstrated that NhhA-triggered Mo differentiation occurred upon engaged Toll-like receptor 1 (TLR1)/TLR2 signaling and extracellular signal-regulated kinase (ERK) and Jun N-terminal protein kinase (JNK) activation and required endogenously produced IL-10 and tumor necrosis factor alpha (TNF-α). Our findings reveal a strategy that might be adopted by N. meningitidis to maintain asymptomatic nasopharyngeal colonization.
IMPORTANCE
Neisseria meningitidis is an opportunistic human-specific pathogen that colonizes the nasopharyngeal mucosa asymptomatically in approximately 10% of individuals. Very little is known about how this bacterium evades immune activation during the carriage stage. Here, we observed that N. meningitidis, via the conserved surface protein NhhA, skewed monocyte differentiation into macrophages with a CD200R(hi) phenotype. Both in vivo and in vitro data demonstrated that these macrophages, upon meningococcal infection, played an important role in forming a homeostatic immune microenvironment through their capacity to eliminate invading bacteria and to generate anti-inflammatory mediators. This work provides novel insight into the mechanisms underlying the commensal persistence of N. meningitidis.
Topics: Adhesins, Bacterial; Animals; Carrier State; Cell Differentiation; Chemokine CCL17; Chemokine CCL22; Chemokines, CC; Disease Models, Animal; Homeostasis; Humans; Immunity, Innate; Interleukin-10; Macrophages; Meningococcal Infections; Mice; Monocytes; Nasopharynx; Neisseria meningitidis; Signal Transduction; Symbiosis; T-Lymphocytes, Regulatory; Toll-Like Receptor 2; Tumor Necrosis Factor-alpha
PubMed: 26884432
DOI: 10.1128/mBio.01670-15 -
European Annals of Otorhinolaryngology,... Dec 2017
Topics: Aged; Anti-Bacterial Agents; Biopsy; Chronic Disease; Diagnosis, Differential; Female; Humans; Laryngoscopy; Levofloxacin; Nasopharyngitis; Nasopharynx; Necrosis; Pigmentation; Treatment Outcome; Ulcer
PubMed: 28673656
DOI: 10.1016/j.anorl.2016.11.013 -
PLoS Pathogens Feb 2017Oropharyngeal mucosal epithelia of fetuses/neonates/infants and the genital epithelia of adults play a critical role in HIV-1 mother-to-child transmission and sexual...
Oropharyngeal mucosal epithelia of fetuses/neonates/infants and the genital epithelia of adults play a critical role in HIV-1 mother-to-child transmission and sexual transmission of virus, respectively. To study the mechanisms of HIV-1 transmission through mucosal epithelium, we established polarized tonsil, cervical and foreskin epithelial cells. Analysis of HIV-1 transmission through epithelial cells showed that approximately 0.05% of initially inoculated virions transmigrated via epithelium. More than 90% of internalized virions were sequestered in the endosomes of epithelial cells, including multivesicular bodies (MVBs) and vacuoles. Intraepithelial HIV-1 remained infectious for 9 days without viral release. Release of sequestered intraepithelial HIV-1 was induced by the calcium ionophore ionomycin and by cytochalasin D, which increase intracellular calcium and disrupt the cortical actin of epithelial cells, respectively. Cocultivation of epithelial cells containing HIV-1 with activated peripheral blood mononuclear cells and CD4+ T lymphocytes led to the disruption of epithelial cortical actin and spread of virus from epithelial cells to lymphocytes. Treatment of epithelial cells with proinflammatory cytokines tumor necrosis factor-alpha and interferon gamma also induced reorganization of cortical actin and release of virus. Inhibition of MVB formation by small interfering RNA (siRNA)-mediated silencing of its critical protein hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) expression reduced viral sequestration in epithelial cells and its transmission from epithelial cells to lymphocytes by ~60-70%. Furthermore, inhibition of vacuole formation of epithelial cells by siRNA-inactivated rabankyrin-5 expression also significantly reduced HIV-1 sequestration in epithelial cells and spread of virus from epithelial cells to lymphocytes. Interaction of the intercellular adhesion molecule-1 of epithelial cells with the function-associated antigen-1 of lymphocytes was important for inducing the release of sequestered HIV-1 from epithelial cells and facilitating cell-to-cell spread of virus from epithelial cells to lymphocytes. This mechanism may serve as a pathway of HIV-1 mucosal transmission.
Topics: Blotting, Western; CD4-Positive T-Lymphocytes; Cervix Uteri; Coculture Techniques; Dendritic Cells; Epithelial Cells; Female; Fluorescent Antibody Technique; Foreskin; HIV Infections; HIV-1; Humans; Leukocytes, Mononuclear; Macrophages; Male; Mucous Membrane; Palatine Tonsil; Transcytosis
PubMed: 28241053
DOI: 10.1371/journal.ppat.1006247 -
PLoS Neglected Tropical Diseases Apr 2021Naja atra is a major venomous snake found in Taiwan. The bite of this snake causes extensive wound necrosis or necrotizing soft tissue infection. Conventional microbial...
An investigation of conventional microbial culture for the Naja atra bite wound, and the comparison between culture-based 16S Sanger sequencing and 16S metagenomics of the snake oropharyngeal bacterial microbiota.
Naja atra is a major venomous snake found in Taiwan. The bite of this snake causes extensive wound necrosis or necrotizing soft tissue infection. Conventional microbial culture-based techniques may fail to identify potential human pathogens and render antibiotics ineffective in the management of wound infection. Therefore, we evaluated 16S Sanger sequencing and next-generation sequencing (NGS) to identify bacterial species in the oropharynx of N. atra. Using conventional microbial culture methods and the VITEK 2 system, we isolated nine species from snakebite wounds. On the basis of the 16S Sanger sequencing of bacterial clones from agar plates, we identified 18 bacterial species in the oropharynx of N. atra, including Morganella morganii, Proteus vulgaris, and Proteus mirabilis, which were also present in the infected bite wound. Using NGS of 16S metagenomics, we uncovered more than 286 bacterial species in the oropharynx of N. atra. In addition, the bacterial species identified using 16S Sanger sequencing accounted for only 2% of those identified through NGS of 16S metagenomics. The bacterial microbiota of the oropharynx of N. atra were modeled better using NGS of 16S metagenomics compared to microbial culture-based techniques. Stenotrophomonas maltophilia, Acinetobacter baumannii, and Proteus penneri were also identified in the NGS of 16S metagenomics. Understanding the bacterial microbiota that are native to the oropharynx of N. atra, in addition to the bite wound, may have additional therapeutic implications regarding empiric antibiotic selection for managing N. atra bites.
Topics: Adult; Aged; Animals; Anti-Bacterial Agents; Bacteria; Female; High-Throughput Nucleotide Sequencing; Humans; Male; Metagenomics; Middle Aged; Naja naja; Oropharynx; RNA, Ribosomal, 16S; Snake Bites; Taiwan; Wound Infection
PubMed: 33857127
DOI: 10.1371/journal.pntd.0009331 -
Korean Journal of Neurotrauma Oct 2018Deep neck infections (DNIs) are mainly caused by dental caries, tonsillitis, and pharyngitis; however, DNIs can also occur after head and neck trauma. A 79-year-old male...
Deep neck infections (DNIs) are mainly caused by dental caries, tonsillitis, and pharyngitis; however, DNIs can also occur after head and neck trauma. A 79-year-old male patient underwent a craniectomy due to an acute subdural hematoma. The patient was unconscious and continued to have a fever, but no clear cause was found. On postoperative day 9, he suddenly showed redness and swelling on the anterior neck. Enhanced computed tomography of the pharynx revealed tracheal necrosis and an abscess in the surrounding area. An incision and drainage were performed and and were identified. The infection was controlled after antibiotic treatment. High endotracheal tube cuff pressure was suspected as the cause of the tracheal infection. Although DNIs are difficult to predict in patients who cannot report their symptoms due to unconsciousness, prevention and rapid diagnosis are important, as DNIs have serious side effects.
PubMed: 30402437
DOI: 10.13004/kjnt.2018.14.2.155 -
Frontiers in Cellular and Infection... 2019Controversy remains concerning the impact of on preterm neonatal morbidity. Prospective single-center study in very low birth weight infants <30 weeks' gestation....
Controversy remains concerning the impact of on preterm neonatal morbidity. Prospective single-center study in very low birth weight infants <30 weeks' gestation. Cord blood and initial nasopharyngeal swabs were screened for and using culture technique and polymerase chain reaction. Neonatal outcomes were followed until death or discharge. Multi-analyte immunoassay provided cord blood levels of inflammatory markers. Using multivariate regression analyses, perinatal exposure was evaluated as risk factor for the development of bronchopulmonary dysplasia (BPD), other neonatal morbidities until discharge and systemic inflammation at admission. 40/103 (39%) infants were positive for in one or both specimens, with being the predominant species. While exposure to alone was not associated with BPD, we found an increased risk of BPD in -positive infants ventilated ≥5 days (OR 1.64; 95% CI 0.12-22.98; = 0.009). Presence of was associated with a 7-fold risk of late onset sepsis (LOS) (95% CI 1.80-27.39; = 0.014). Moreover, -positive infants had higher I/T ratios ( 0.39; 95% CI 0.08-0.71; = 0.014), increased levels of interleukin (IL)-17 ( 0.16; 95% CI 0.02-0.30; = 0.025) and matrix metalloproteinase 8 ( 0.77; 95% CI 0.10-1.44; = 0.020), decreased levels of IL-10 ( -0.77; 95% CI -1.58 to -0.01; = 0.043) and increased ratios of Tumor necrosis factor-α, IL-8, and IL-17 to anti-inflammatory IL-10 ( = 03, = 0.012, < 0.001). Positive screening was not associated with BPD. However, exposure contributed to BPD in infants ventilated ≥5 days and conferred an increased risk of LOS and imbalanced inflammatory cytokine responses.
Topics: Female; Fetal Blood; Humans; Infant, Newborn; Infant, Premature; Late Onset Disorders; Lung Injury; Male; Nasopharynx; Neonatal Sepsis; Prospective Studies; Survival Analysis; Treatment Outcome; Ureaplasma; Ureaplasma Infections; Ureaplasma urealyticum
PubMed: 31001484
DOI: 10.3389/fcimb.2019.00068 -
PloS One 2018Mucopolysaccharide diseases are a group of lysosomal storage disorders caused by deficiencies of hydrolase enzymes, leading to pathological glycosaminoglycan...
INTRODUCTION
Mucopolysaccharide diseases are a group of lysosomal storage disorders caused by deficiencies of hydrolase enzymes, leading to pathological glycosaminoglycan accumulation. A number of mucopolysaccharidosis (MPS) types are characterised by severe airway disease, the aetiology of which is poorly understood. There is ongoing evidence of significant clinical disease in the long-term despite disease modifying therapeutic strategies, including enzyme-replacement therapy (ERT). To provide a better understanding of this aspect of disease, we have characterised extracellular matrix (ECM) and inflammatory alterations in adenotonsillar tissue samples from 8 MPS patients.
METHODS
Adenotonsillar samples from MPS I, IVA and VI ERT treated patients and from a single enzyme naïve MPS IIIA individual were compared to non-affected control samples using quantitative immunohistochemistry, qPCR and biochemical analysis.
RESULTS
Significantly increased lysosomal compartment size and total sulphated glycosaminoglycan (p = 0.0007, 0.02) were identified in patient samples despite ERT. Heparan sulphate glycosaminoglycan was significantly elevated in MPS I and IIIA (p = 0.002), confirming incomplete reversal of disease. Collagen IV and laminin α-5 (p = 0.002, 0.0004) staining demonstrated increased ECM deposition within the reticular and capillary network of MPS samples. No significant change in the expression of the pro-inflammatory cytokines IL-1α, IL-6 or TNF-α was seen compared to control.
CONCLUSION
This study suggests a role for ECM remodelling contributing to the obstructive phenotype of airway disease in MPS. Current therapeutic strategies with ERT fail to normalise these pathological alterations within adenotonsillar samples. Our findings lend novel insight into the pathological cascade of events, with primarily structural rather than inflammatory changes contributing to the continuing phenotype seen in patients despite current therapeutic regimes.
Topics: Adenoids; Child; Child, Preschool; Enzyme Replacement Therapy; Extracellular Matrix; Female; Humans; Infant; Inflammation Mediators; Interleukin-1alpha; Interleukin-6; Male; Mucopolysaccharidoses; Mucopolysaccharidosis I; Mucopolysaccharidosis III; Mucopolysaccharidosis IV; Mucopolysaccharidosis VI; Palatine Tonsil; Tumor Necrosis Factor-alpha
PubMed: 30226843
DOI: 10.1371/journal.pone.0203216 -
Journal of Dairy Science Aug 2019Microbiome modulators such as probiotics are known to modulate oral diseases. Very few probiotics are commercially available for use in the oral cavity. In this context,...
Microbiome modulators such as probiotics are known to modulate oral diseases. Very few probiotics are commercially available for use in the oral cavity. In this context, we selected human-origin Lactobacillus salivarius AR809 as a promising oropharyngeal probiotic and characterized its functional and immunomodulatory properties. Results demonstrated that AR809 could efficiently adhere to pharyngeal epithelial FaDu cells, antagonize Staphylococcus aureus, adapt to the oral environment, and modulate host innate immunity by inducing potentially protective effects. Particularly, AR809 diminished proinflammatory activity by enhancing the production of IL10 and inhibiting the expression of tumor necrosis factor-α, IL1B, inducible nitric oxide synthase, and RELA. Finally, we observed that AR809 grew efficiently when cultured in milk, suggesting that the preparation of a fermented milk product containing AR809 could be a practical way to administer this probiotic to humans. In conclusion, AR809 has high potential to adhere to the pharyngeal mucosa and could be applied in novel milk-based probiotic fermented food products.
Topics: Animals; Bacterial Adhesion; Cultured Milk Products; Epithelium; Humans; Immunity; Inflammation; Ligilactobacillus salivarius; Mouth; Pharynx; Probiotics; Tumor Necrosis Factor-alpha
PubMed: 31178178
DOI: 10.3168/jds.2018-16117 -
The Journal of International Medical... Sep 2018Objective The present study was performed to investigate the relationships between swallowing outcomes and lesion location, bolus characteristics, and age in patients...
UNLABELLED
Objective The present study was performed to investigate the relationships between swallowing outcomes and lesion location, bolus characteristics, and age in patients with subcortical stroke.
PATIENTS
Patients with subcortical and insular stroke (mean age, 57.38 ± 12.71 years) were investigated. All patients (n = 21) completed both brain magnetic resonance imaging studies and videofluoroscopic swallowing studies. Main Outcome Measures The oral transit duration, pharyngeal transit duration (PTD), laryngeal response duration, and Penetration-Aspiration Scale (PAS) score were applied to examine the efficiency of propulsion and airway protection in three swallowing tasks. Path analyses were performed to assess the relationships between swallowing outcomes and lesion location, age, bolus viscosity, and bolus volume. Results Caudate nucleus (CN) lesions were associated with higher PAS scores. Insular lesions were associated with a longer PTD. Advanced age was associated with a longer PTD. Bolus viscosity significantly moderated the association between CN lesions and higher PAS scores. Conclusions In the present cohort, CN lesions impacted airway protection and insular lesions impacted pharyngeal transit. An increased bolus viscosity reduced the aspiration severity. These results suggest that lesion location is an important indicator to predict subsequent dysphagia in patients with subcortical stroke.
Topics: Adult; Aged; Aged, 80 and over; Brain Infarction; Caudate Nucleus; Cerebral Cortex; Deglutition; Deglutition Disorders; Female; Fluoroscopy; Humans; Intracranial Hemorrhages; Magnetic Resonance Imaging; Male; Middle Aged; Pharynx; Stroke
PubMed: 29865925
DOI: 10.1177/0300060518775290 -
Cirugia Pediatrica : Organo Oficial de... Jan 2021Caustic burns still cause complex esophageal lesions in the pediatric population. However, therapeutic possibilities in severe cases are limited. A surgical approach...
INTRODUCTION
Caustic burns still cause complex esophageal lesions in the pediatric population. However, therapeutic possibilities in severe cases are limited. A surgical approach allowing for a longer neoesophagus, an isoperistaltic esophagus, and a better vascularization, with a lower risk of complications such as necrosis, stenosis, or perforation, is proposed.
CLINICAL CASE
16-month-old patient who accidentally ingested caustic soda. This caused a IIIb degree burn compromising the pharynx down to the stomach. Esophageal replacement with an isoperistaltic gastric tube was carried out, which allowed for a neoesophagus of appropriate length, an optimal vascularization for the graft, and physiological peristalsis.
COMMENTS
The surgical approach proposed allows the esophagus to be irrigated from the right gastro-omental artery, thus preserving irrigation of the greater curvature. It also allows for a longer esophagus, and thanks to anatomical positioning, for physiological peristalsis.
Topics: Burns, Chemical; Caustics; Child; Esophageal Stenosis; Humans; Infant; Stomach
PubMed: 33507643
DOI: No ID Found