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Frontiers in Immunology 2021In mucosa such as tonsil, antibody-producing plasmocytes (PCs) lie in sub-epithelium space, which is thought to provide a suitable environment for their survival. A...
In mucosa such as tonsil, antibody-producing plasmocytes (PCs) lie in sub-epithelium space, which is thought to provide a suitable environment for their survival. A proliferation inducing ligand (APRIL) is one key survival factor for PCs present in this area. According to staining, apical epithelial cells produced APRIL, and the secreted product had to migrate all through the stratified surface epithelium to reach basal cells. A similar process also occurred in the less-organized crypt epithelium. Tonsil epithelial cells captured secreted APRIL, thanks to their surface expression of the APRIL coreceptor, either syndecan-1 or -4 depending on their differentiation stage. In the most basal epithelial cells, secreted APRIL accumulated inside secretory lamp-1 vesicles in a polarized manner, facing the sub-epithelium. The tonsil epithelium upregulated APRIL production by apical cells and secretion by basal cells upon Toll-like receptor stimulation. Furthermore, LPS-stimulated epithelial cells sustained PC survival in a secreted APRIL-dependent manner. Taken together, our study shows that the tonsil epithelium responds to pathogen sensing by a polarized secretion of APRIL in the sub-epithelial space, wherein PCs reside.
Topics: Biomarkers; Cell Line; Cell Polarity; Epithelium; Heparan Sulfate Proteoglycans; Humans; Immunohistochemistry; Lysosomal-Associated Membrane Protein 1; Mucous Membrane; Palatine Tonsil; Toll-Like Receptors; Tumor Necrosis Factor Ligand Superfamily Member 13
PubMed: 34484218
DOI: 10.3389/fimmu.2021.715724 -
The American Journal of Case Reports Apr 2020BACKGROUND The prevalence of aberrant internal carotid artery (ICA) is extremely low in the general population. It commonly occurs in the neck. Close proximity of the... (Review)
Review
BACKGROUND The prevalence of aberrant internal carotid artery (ICA) is extremely low in the general population. It commonly occurs in the neck. Close proximity of the pulsatile submucosal mass of the aberrant ICA to the nasopharyngeal wall is dangerous. The complications include severe or fatal hemorrhage resulting from a missed diagnosis before intervention in this area, including tonsillectomy, adenoidectomy, eustachian tube dilation, oropharynx biopsy or resection, tracheal intubation, and neck surgery. We report the case of a 66-year-old woman who had a pulsatile mass of the kinked ICA in close proximity to the lateral nasopharyngeal wall, and provide a review of the literature. CASE REPORT The patient presented to our Ear, Nose, and Throat Clinic with persistent cough with phlegm. Endoscopic examination revealed an abnormal pulsatile mass in the lateral nasopharyngeal wall. Subsequent contrast-enhanced computed tomography angiography confirmed the presence of unilateral acute maxillary sinusitis, and a high-grade kinked submucosal mass of the ICA in the ipsilateral nasopharyngeal wall, concomitant with stenosis of the left ICA and left middle cerebral artery occlusion. CONCLUSIONS Pulsating and extremely high-grade kinking of the ICA in the lateral nasopharyngeal wall is a particularly dangerous condition. Clinicians must always consider the possibility of hemorrhage during surgery, especially in older women with arteriosclerosis. Otolaryngologists should perform comprehensive visual examinations before deciding on surgery or other medical interventions in the neck, to prevent severe or fatal hemorrhage as far as possible.
Topics: Aged; Carotid Artery, Internal; Carotid Stenosis; Computed Tomography Angiography; Cough; Female; Humans; Infarction, Middle Cerebral Artery; Nasopharynx
PubMed: 32282788
DOI: 10.12659/AJCR.921967 -
The Journal of Experimental Medicine Jan 1956Rabbits subjected to single pharyngeal infections with group A streptococci developed cardiac lesions characterized by myofiber necrosis and a non-granulocytic cellular...
Rabbits subjected to single pharyngeal infections with group A streptococci developed cardiac lesions characterized by myofiber necrosis and a non-granulocytic cellular reaction with histiocytes, lymphocytes, and Anitschkow myocytes. The histopathologic changes were demonstrable in some animals within 24 hours of inoculation, apparently were maximal 72 hours after induction of infection (at which time they were seen in the hearts of all nine rabbits studied), and thereafter healed in the course of the following 2 weeks. The extent of involvement was variable, and with healing the necrotic areas were replaced by fibrous tissue. When intradermal infections with the same organisms were produced in rabbits, cardiac lesions, indistinguishable from those observed in the pharyngeally infected group, appeared in a much smaller number of animals. The hearts of five of six rabbits sacrificed a month or more following the last of a series of streptococcal pharyngeal infections exhibited lesions characterized chiefly by fibrosis, although mononuclear cellular infiltrations were also noted. In these repetitively infected animals the presence of occasional multinucleated giant cells and a few small foci of calcification were features not encountered in the single infection group. In a second series of rabbits sacrificed 3 days after the last of three pharyngeal infections with different strains of streptococci, acute as well as more chronic changes were observed. In none of the lesions in rabbits subjected to single or multiple streptococcal infections were bacteria demonstrable, either in histologic sections or in cultures of myocardial tissue. A large number of control animals was studied concomitantly, and in only one instance was a lesion, considered comparable to those described in the streptococcal series, encountered. The implications of these findings, particularly in terms of the non-suppurative sequelae of streptococcal infections in man, are discussed.
Topics: Animals; Incidence; Myocarditis; Myocardium; Necrosis; Pharyngeal Diseases; Pharynx; Rabbits; Streptococcal Infections; Streptococcus pyogenes
PubMed: 13278463
DOI: 10.1084/jem.103.1.173 -
Journal of Comparative Pathology Apr 1992The potential involvement of the pharyngeal tonsil in the pathogenesis of bovine herpesvirus-1 (BHV-1) infection was examined in neonatal and weanling calves infected by...
The potential involvement of the pharyngeal tonsil in the pathogenesis of bovine herpesvirus-1 (BHV-1) infection was examined in neonatal and weanling calves infected by intranasal aerosol. Calves were monitored from days 1 to 5, and on day 6 (neonates) or 8 (weanlings) and, in a second trial at day 4.5, by histology, electron microscopy, immunocytochemistry and virus isolation. Mucosal lesions of neonates were similar to, but less extensive than, those of weanling calves. Loss of microvilli and goblet cells, with minimal epithelial erosions as early as day 1, progressed to necrosis of epithelium and adjacent lymphoid tissue, and leucocyte exudation. Lesions and clinical disease were progressive up to and including day 6 in neonates, but resolving in weanlings on days 5 and 8. By transmission electron microscopy, the physical characteristics of the phagocytic cells appeared similar in both age groups, and viral replication was not identified in leucocytes. Virus was isolated from, or found by immunocytochemistry in, the pharyngeal tonsil of all calves examined, except for two weanlings on days 1 and 8. Virus as detected by immunocytochemistry was restricted to epithelium and superficial lymphoid tissue in neonates, but was found in deep lymphoid tissue around germinal centres in weanlings. The study showed that the pharyngeal tonsil is readily infected with BHV-1 and may be an important lymphoid tissue for early anti-viral responses. The delayed inflammatory response and reduced viral clearance may contribute to the increased susceptibility of neonatal calves to fatal BHV-1 infections.
Topics: Animals; Animals, Newborn; Cattle; Immunohistochemistry; Infectious Bovine Rhinotracheitis; Microscopy, Electron; Microscopy, Electron, Scanning; Palatine Tonsil; Weaning
PubMed: 1602058
DOI: 10.1016/0021-9975(92)90053-w -
Clinical and Diagnostic Laboratory... Nov 2004Recurrent or chronic adenotonsillar infections mainly affect children and frequently involve otherwise healthy subjects. Therefore, having excluded systemic...
Recurrent or chronic adenotonsillar infections mainly affect children and frequently involve otherwise healthy subjects. Therefore, having excluded systemic immunological deficiencies, this disease may be due to a local dysfunction of the epithelial structures at either the rhino or oropharyngeal level. The aim of the present investigation was to analyze structural and immunological aspects of tonsils and adenoids in subjects who underwent adenotonsillectomy because of recurrent inflammatory episodes with fever. Histological studies and analyses of the cytokine patterns were carried out in palatine tonsils and adenoid samples from 105 patients who underwent adenoidectomy and bilateral extracapsular tonsillectomy for chronic inflammatory hypertrophy of these organs; 46 of the 105 cases examined presented hyperkeratosis of the crypt epithelium; in the remaining 59, the epithelium was hyperplastic with no signs of keratosis. Scanning electron microscopy revealed a continuous epithelial surface of polygon-shaped flattened cells with fissures towards the cryptic depressions. Titration of interleukin-1beta and tumor necrosis factor alpha in serum and tissues demonstrated higher concentrations in the adenotonsillar specimens, whereas the rise in interleukin-6 was more modest.
Topics: Adenoidectomy; Adenoids; Adolescent; Child; Child, Preschool; Chronic Disease; Cytokines; Female; Humans; Hypertrophy; Inflammation; Male; Palatine Tonsil; Tonsillectomy; Tonsillitis
PubMed: 15539521
DOI: 10.1128/CDLI.11.6.1154-1157.2004 -
AIDS (London, England) Jan 2009To determine how antiretroviral therapy (ART) or HAART affects the expression of apoptotic ligands and their death receptors in the blood and lymphoid tissues of...
OBJECTIVE
To determine how antiretroviral therapy (ART) or HAART affects the expression of apoptotic ligands and their death receptors in the blood and lymphoid tissues of HIV-infected patients and simian immunodeficiency virus-infected macaques.
METHODS
We analyzed the mRNA expression of death molecules [tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and FasL] and their receptors (DR5 and Fas) in blood and tonsils from HIV-infected patients (HIV positive), HIV-infected patients receiving HAART and HIV-uninfected (HIV negative) donors in a cross-sectional study. We comparatively analyzed mRNA expression of TRAIL and DR5 in blood and lymph nodes collected longitudinally from simian immunodeficiency virus-infected macaques before and after ART.
RESULTS
Expression of TRAIL, FasL, DR5 and Fas was elevated in circulating CD4 T cells from a group of HIV-positive patients as compared with that from both HIV-negative donors and HAART patients. In a different study group, TRAIL, FasL, DR5 and Fas were increased in tonsils of HIV-positive patients as compared with HIV-negative donors and HAART patients. However, tonsils from HAART patients showed reduced expression of TRAIL and FasL but not DR5 and Fas as compared with HIV-positive patients. Similarly, data obtained in a longitudinal study of simian immunodeficiency virus-infected macaques showed that ART reduced both TRAIL and DR5 in peripheral blood but only TRAIL and not DR5 in lymph nodes from the same animals.
CONCLUSION
These findings suggest that HAART or ART is ineffective in reducing the expression of apoptotic death receptors in lymphoid tissue. However, analysis limited to blood leukocytes may not reveal such a defect. Our results highlight the persistence of an underlying immunologic condition that may prevent therapy-induced restoration of CD4 T cells in lymphoid tissue.
Topics: Animals; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Cross-Sectional Studies; Fas Ligand Protein; Gene Expression Regulation; HIV Infections; Humans; Lymph Nodes; Lymphoid Tissue; Macaca; Palatine Tonsil; RNA, Messenger; Receptors, Death Domain; Simian Acquired Immunodeficiency Syndrome; TNF-Related Apoptosis-Inducing Ligand
PubMed: 19050384
DOI: 10.1097/QAD.0b013e32831cb907 -
The Journal of Biological Chemistry Jan 2011Human serum albumin (HSA) is the dominating protein in human plasma. Many bacterial species, especially streptococci, express surface proteins that bind HSA with high...
Human serum albumin (HSA) is the dominating protein in human plasma. Many bacterial species, especially streptococci, express surface proteins that bind HSA with high specificity and affinity, but the biological consequences of these protein-protein interactions are poorly understood. Group G streptococci (GGS), carrying the HSA-binding protein G, colonize the skin and the mucosa of the upper respiratory tract, mostly without causing disease. In the case of bacterial invasion, pro-inflammatory cytokines are released that activate the epithelium to produce antibacterial peptides, in particular the chemokine MIG/CXCL9. In addition, the inflammation causes capillary leakage and extravasation of HSA and other plasma proteins, environmental changes at the epithelial surface to which the bacteria need to respond. In this study, we found that GGS adsorbed HSA from both saliva and plasma via binding to protein G and that HSA bound to protein G bound and inactivated the antibacterial MIG/CXCL9 peptide. Another surface protein of GGS, FOG, was found to mediate adherence of the bacteria to pharyngeal epithelial cells through interaction with glycosaminoglycans. This adherence was not affected by activation of the epithelium with a combination of IFN-γ and TNF-α, leading to the production of MIG/CXCL9. However, at the activated epithelial surface, adherent GGS were protected against killing by MIG/CXCL9 through protein G-dependent HSA coating. The findings identify a previously unknown bacterial survival strategy that helps to explain the evolution of HSA-binding proteins among bacterial species of the normal human microbiota.
Topics: Antiviral Agents; Bacterial Adhesion; Bacterial Proteins; Capillary Permeability; Cells, Cultured; Chemokine CXCL9; Epithelial Cells; Glycosaminoglycans; Interferon-gamma; Microbial Viability; Pharynx; Protein Binding; Serum Albumin; Streptococcus mutans; Tumor Necrosis Factor-alpha
PubMed: 21098039
DOI: 10.1074/jbc.M110.148171 -
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 -
MBio Oct 2013Biofilms are thought to play an important role during colonization of the nasopharynx by Streptococcus pneumoniae, yet how they form in vivo and the determinants...
UNLABELLED
Biofilms are thought to play an important role during colonization of the nasopharynx by Streptococcus pneumoniae, yet how they form in vivo and the determinants responsible remain unknown. Using scanning electron microscopy, we show that biofilm aggregates of increasing complexity form on murine nasal septa following intranasal inoculation. These biofilms were highly distinct from in vitro biofilms, as they were discontiguous and appeared to incorporate nonbacterial components such as intact host cells. Biofilms initially formed on the surface of ciliated epithelial cells and, as cells were sloughed off, were found on the basement membrane. The size and number of biofilm aggregates within nasal lavage fluid were digitally quantitated and revealed strain-specific capabilities that loosely correlated with the ability to form robust in vitro biofilms. We tested the ability of isogenic mutants deficient in CbpA, pneumolysin, hydrogen peroxide, LytA, LuxS, CiaR/H, and PsrP to form biofilms within the nasopharynx. This analysis revealed that CiaR/H was absolutely required for colonization, that PsrP and SpxB strongly impacted aggregate formation, and that other determinants affected aggregate morphology in a modest fashion. We determined that mice colonized with ΔpsrP mutants had greater levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-1β, and KC in nasal lavage fluid than did mice colonized with wild-type controls. This phenotype correlated with a diminished capacity of biofilm pneumococci to invade host cells in vitro despite enhanced attachment. Our results show that biofilms form during colonization and suggest that they may contribute to persistence through a hyperadhesive, noninvasive state that elicits a dampened cytokine response.
IMPORTANCE
This work demonstrates the first temporal characterization of Streptococcus pneumoniae biofilm formation in vivo. Our results show that the morphology of biofilms formed by both invasive and noninvasive clinical isolates in vivo is distinct from that of formed biofilms in vitro, yet propensity to form biofilms in vivo loosely correlates with the degree of in vitro biofilm formation on a microtiter plate. We show that host components, including intact host cells, influence the formation of in vivo structures. We also found that efficient biofilm formation in vivo requires multiple bacterial determinants. While some factors are essential for in vivo biofilm formation (CiaRH, PsrP, and SpxB), other factors are less critical (CbpA, LytA, LuxS, and pneumolysin). In comparison to their planktonic counterparts, biofilm pneumococci are hyperadhesive but less invasive and elicit a weaker proinflammatory cytokine response. These findings give insight into the requirements for and potential role of biofilms during prolonged asymptomatic colonization.
Topics: Animals; Bacterial Proteins; Biofilms; Female; Humans; Mice; Mice, Inbred BALB C; Nasopharynx; Pneumococcal Infections; Species Specificity; Streptococcus pneumoniae; Virulence
PubMed: 24129258
DOI: 10.1128/mBio.00745-13 -
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