Project description:BACKGROUND:The relationships between tonsillar immune responses, and viral infection and allergy are incompletely known. OBJECTIVE:To study intratonsillar/nasopharyngeal virus detections and in vivo expressions of T-cell- and innate immune response-specific cytokines, transcription factors, and type I/II/III interferons in human tonsils. METHODS:Palatine tonsil samples were obtained from 143 elective tonsillectomy patients. Adenovirus, bocavirus-1, coronavirus, enteroviruses, influenza virus, metapneumovirus, parainfluenza virus, rhinovirus, and respiratory syncytial virus were detected using PCR. The mRNA expression levels of IFN-?, IFN-?, IFN-?, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-?, FOXP3, GATA3, RORC2, and Tbet were directly analyzed by quantitative RT-PCR. RESULTS:Fifty percentage of subjects reported allergy, 59% had ?1 nasopharyngeal viruses, and 24% had ?1 intratonsillar viruses. Tonsillar virus detection showed a strong negative association with age; especially rhinovirus or parainfluenza virus detection showed positive association with IFN-? and Tbet expressions. IL-37 expression was positively associated with atopic dermatitis, whereas IFN-?, IL-13, IL-28, and Tbet expressions were negatively associated with allergic diseases. Network analyses demonstrated strongly polarized clusters of immune regulatory (IL-10, IL-17, TGF-?, FOXP3, GATA3, RORC2, Tbet) and antiviral (IFN-?, IFN-?, IL-28, IL-29) genes. These two clusters became more distinctive in the presence of viral infection or allergy. A negative correlation between antiviral cytokines and IL-10, IL-17, IL-37, FOXP3, and RORC2 was observed only in the presence of viruses, and interestingly, IL-13 strongly correlated with antiviral cytokines. CONCLUSIONS:Tonsillar cytokine expression is closely related to existing viral infections, age, and allergic illnesses and shows distinct clusters between antiviral and immune regulatory genes.
Project description:The comprehension of unconventional immune functions of tonsillar B cells, their role in tolerance induction and protective immune responses, is crucial to unveil the dynamic interactions of the upper aero digestive tract with polymicrobial commensal flora and pathogens, in health and disease. Here, we describe the kinetics of IL10 intracellular expression and compare it with that of cytokines known to be produced by tonsillar B cells. Additionally, we detected a relevant proportion of IL17-expressing tonsillar B cells, which has not previously been reported. We immunophenotyped tonsillar IL10-expressing B cells (B10) and observed IL10 production in activated B cells at every developmental stage. Finally, we identified a relationship between decreased B10 percentages, increased proportion of the germinal centre (GC) population and hypertrophied tonsils (HT). Our findings provide greater insight into the role of B10 in GC reactions and characterized their involvement in the pathogenesis of tonsillar dysfunction.
Project description:Tonsils provide an innovative in vivo model for investigating immune response to infections and allergens. However, data are scarce on the differences in tonsillar virus infections and immune responses between patients with tonsillar hypertrophy or recurrent tonsillitis. We investigated the differences in virus detection and T cell and interferon gene expression in patients undergoing tonsillectomy due to tonsillar hypertrophy or recurrent tonsillitis.Tonsils of 89 surgical patients with tonsillar hypertrophy (n?=?47) or recurrent tonsillitis (n?=?42) were analysed. Patients were carefully characterized clinically. Standard questionnaire was used to asses preceding and allergy symptoms. Respiratory viruses were analysed in tonsils and nasopharynx by PCR. Quantitative real-time PCR was used to analyse intratonsillar gene expressions of IFN-?, IFN-?, IFN-?, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-?, FOXP3, GATA3, RORC2 and Tbet.Median age of the subjects was 15 years (range 2-60). Patients with tonsillar hypertrophy were younger, smoked less often, had less pollen allergy and had more adenovirus, bocavirus-1, coronavirus and rhinovirus in nasopharynx (all P?<?0.05). Only bocavirus-1 was more often detected in hypertrophic tonsils (P?<?0.05). In age-adjusted analysis, tonsillar hypertrophy was associated with higher mRNA expressions of IL-37 (P?<?0.05).Intratonsillar T cell and interferon gene expressions appeared to be relatively stable for both tonsillar hypertrophy and recurrent tonsillitis. Of the studied cytokines, only newly discovered anti-inflammatory cytokine IL-37, was independently associated with tonsillar hypertrophy showing slightly stronger anti-inflammatory response in these patients.
Project description:In the past few years, eleven new human viruses have joined the two previously known members JCPyV and BKPyV of the Polyomaviridae family, by virtue of molecular methods. Serology data suggest that infections with human polyomaviruses (HPyVs) occur since childhood and the viruses are widespread in the general population. However, the viral persistence sites and transmission routes are by and large unknown. Our previous studies demonstrated that the four new HPyVs - KIPyV, WUPyV, MCPyV and TSPyV - were present in the tonsils, and suggested lymphoid tissue as a persistent site of these emerging human viruses. We developed a Luminex-based multiplex assay for simultaneous detection of all 13 HPyVs known, and explored their occurrence in tonsillar tissues of children and adults mostly with tonsillitis or tonsillar hypertrophy.We set up and validated a new Luminex-based multiplex assay by using primer pairs and probes targeting the respective HPyV viral protein 1 (VP1) genes. With this assay we tested 78 tonsillar tissues for DNAs of 13 HPyVs.The multiplex assay allowed for simultaneous detection of 13 HPyVs with high analytical sensitivity and specificity, with detection limits of 100-102 copies per microliter, and identified correctly all 13 target sequences with no cross reactions. HPyV DNA altogether was found in 14 (17.9%) of 78 tonsils. The most prevalent HPyVs were HPyV6 (7.7%), TSPyV (3.8%) and WUPyV (3.8%). Mixed infection of two HPyVs occurred in one sample.The Luminex-based HPyV multiplex assay appears highly suitable for clinical diagnostic purposes and large-scale epidemiological studies. Additional evidence was acquired that the lymphoid system plays a role in HPyV infection and persistence. Thereby, shedding from this site during reactivation might take part in transmission of the newly found HPyVs.
Project description:Recently, submandibular abscesses associated with Actinomyces denticolens have been reported in horses. The actinomycotic clumps have been observed in the tonsillar crypts. The aim of this study was to demonstrate colonisation of A denticolens in equine tonsils. Twelve equine tonsils obtained from a slaughterhouse were divided into two parts for histopathological examination and for isolation of A denticolens. When actinomycotic clumps were found in these tonsillar crypts, immunohistochemistry using hyperimmune serum against A denticolens (DMS 20671) was performed on the serial sections. To determine whether Actinomyces-like bacteria isolated using immunoantigenic separation technique were A denticolens, the isolates were analysed for the 16S rRNA gene sequence. Actinomycotic clumps were found in the tonsillar crypts of 11 (91.7 per cent) horses. The clumps were of the saprophytic type accompanied with the feedstuffs, but a few clumps were surrounded by inflammatory cells. A denticolens antigens were immunodetected not only in the clumps of 11 (100 per cent) tonsils, but also in the tonsillar parenchyma. Six isolates obtained from four tonsils showed 99.7-99.9 per cent similarity to A denticolens in the 16S rRNA gene sequence. In horses, the colonisation sites of A denticolens are the tonsils, thus the authors suggest that the tonsils provide the intrinsic infection site for A denticolens.
Project description:<h4>Introduction</h4>Kimura's disease is a rare inflammatory disorder of unknown cause, commonly seen in young Asian males. <i>Case Report</i>. A 61-year-old male patient presented with a history of right tonsillar mass and cervical lymphadenopathy. The patient underwent hematological investigation and imaging followed by resection of tonsillar mass. Based on histopathological and subsequent immunohistochemistry reports, the case was diagnosed as Kimura's disease of the tonsil. <i>Discussion</i>. Kimura's disease commonly presents as painless subcutaneous masses in the head and neck region or cervical lymphadenopathy. Kimura's disease presenting as a tonsillar mass is a very rare condition. Patients usually have peripheral eosinophilia and elevated levels of serum IgE. The diagnosis is based on the clinical and histopathologic findings in a biopsy of the mass and/or lymph node along with elevated peripheral eosinophil and serum IgE level.<h4>Conclusion</h4>The clinical presentation of Kimura's disease is highly variable. Kimura's disease should be considered as a differential diagnosis in patients presenting with a tonsillar mass. A high index of suspicion along with histopathological examination helps in the early diagnosis and management. Surgical excision is the treatment of choice.
Project description:Surgically removed palatine tonsils provide a conveniently accessible source of T and B lymphocytes to study the interplay between foreign pathogens and the host immune system. In this study we have characterised the distribution of human adenovirus (HAdV), Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) in purified tonsillar T and B cell-enriched fractions isolated from three patient age groups diagnosed with tonsillar hypertrophy and chronic/recurrent tonsillitis. HAdV DNA was detected in 93 out of 111 patients (84%), while EBV DNA was detected in 58 patients (52%). The most abundant adenovirus type was HAdV-5 (68%). None of the patients were positive for HCMV. Furthermore, 43 patients (39%) showed a co-infection of HAdV and EBV. The majority of young patients diagnosed with tonsillar hypertrophy were positive for HAdV, whereas all adult patients diagnosed with chronic/recurrent tonsillitis were positive for either HAdV or EBV. Most of the tonsils from patients diagnosed with either tonsillar hypertrophy or chronic/recurrent tonsillitis showed a higher HAdV DNA copy number in T compared to B cell-enriched fraction. Interestingly, in the majority of the tonsils from patients with chronic/recurrent tonsillitis HAdV DNA was detected in T cells only, whereas hypertrophic tonsils demonstrated HAdV DNA in both T and B cell-enriched fractions. In contrast, the majority of EBV positive tonsils revealed a preference for EBV DNA accumulation in the B cell-enriched fraction compared to T cell fraction irrespective of the patients' age.
Project description:Background:Rhinovirus A and C infections are important contributors to asthma induction and exacerbations. No data exist on the interaction of local immune responses in rhinovirus infection. Therefore, we aimed to determine the tonsillar immune responses according to rhinovirus A, B and C infections. Methods:We collected tonsillar samples, nasopharyngeal aspirates and peripheral blood from 42 rhinovirus positive tonsillectomy patients. Fifteen respiratory viruses or their types were investigated from nasopharynx and tonsil tissue, and rhinovirus species were typed. The expression of 10 cytokines and 4 transcription factors (IFN-?, IFN-?, IFN-?, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-?, FOXP3, GATA3, RORC2 and Tbet) were studied from tonsil tissue by quantitative PCR. A standard questionnaire of respiratory symptoms and health was filled by the patient or his/her guardian. The patients were divided into three groups by the determination of rhinovirus species. Results:Overall, 16 patients had rhinovirus A, 12 rhinovirus B and 14 rhinovirus C infection. In rhinovirus B positive group there were significantly less men (P?=?0.0072), less operated in spring (P?=?0.0096) and more operated in fall (P?=?0.030) than in rhinovirus A or C groups. Rhinovirus A positive patients had more respiratory symptoms (P?=?0.0074) and particularly rhinitis (P?=?0.036) on the operation day. There were no significant differences between the groups in virus codetection. In adjusted analysis, rhinovirus C infections were associated with increased IFN-? (P?=?0.045) and decreased RORC2 expression (P?=?0.025). Conclusions:Rhinovirus species associated differently with clinical characteristics and tonsillar cytokine responses.
Project description:Immunoglobulin A nephropathy (IgAN) involves repeated events of gross haematuria with concurrent upper airway infections. The mucosal immune system, especially the tonsil, is considered the initial site of inflammation, although the role of the tonsillar microbiota has not been established in IgAN. In this study, we compared the tonsillar microbiota of patients with IgAN (n?=?21) and other glomerular diseases (n?=?36) as well as, healthy controls (n?=?23) from three medical centres in Korea. The microbiota was analysed from tonsil swabs using the Illumina MiSeq system based on 16S rRNA gene. Tonsillar bacterial diversity was higher in IgAN than in other glomerular diseases, although it did not differ from that of healthy controls. Principal coordinates analysis revealed differences between the tonsillar microbiota of IgAN and both healthy and disease controls. The proportions of Rahnella, Ruminococcus_g2, and Clostridium_g21 were significantly higher in patients with IgAN than in healthy controls (corrected p?<?0.05). The relative abundances of several taxa were correlated with the estimated glomerular filtration rate, blood urea nitrogen, haemoglobin, and serum albumin levels. Based on our findings, tonsillar microbiota may be associated with clinical features and possible immunologic pathogenesis of IgAN.
Project description:Lingual tonsillar hypertrophy is an unusual presentation of voice change. If managed incorrectly this group of patients has the potential to deteriorate significantly causing airway obstruction and potentially death.