Tonsillar transcriptional profiles in atopic and non‐atopic subjects

Background: Emerging research suggests that local lymphatic tissue such as tonsils have important role in regulating the immune responses. However, allergen sensitization-induced alterations in transcriptome of tonsils are not known. Objectives: To examine the key differences in tonsillar gene expression between atopic and non-atopic subjects and further by type of sensitization. Methods: RNA-sequencing was performed on 52 tonsillar samples from atopic and non-atopic tonsillectomy patients. Sensitization to common food- and aero-allergen was defined by allergen specific IgE. Following groups were studied: (1) aero- and food-allergen sensitized (AS+FS) versus non-sensitized (NS), (2) aeroallergen-sensitized (AS) versus food-allergen sensitized (FS), (3) AS versus NS, (4) FS versus NS. Bioinformatics analysis was done using DESeq2(v3.10.2), WGCNA and GATK pipeline in R software (v3.3.1). Protein-protein interaction network was made from String database. Results: We studied 13 aeroallergen-sensitized, 6 food-allergen sensitized, 4 both food-and aero-allergen-sensitized and 29 non-sensitized tonsillectomy patients. Overall, 697 unique differentially expressed genes (DEGs) were detected in all sensitized subgroups including chemokines (CXCL2, CXCL8, CXCL10, CXCL11), IL-20RA, MUC1 and MUC20. When comparing different groups, the gene expression profiles overlapped except the AS versus FS group comparison, suggesting significantly different gene expression between the two sensitization subgroups. Furthermore, aeroallergen-sensitized subjects had more prominent immune responses compared with non-sensitized and food-allergen sensitized subjects including gene expression for IL-17 pathway and Toll-like receptor signalling pathway. Conclusion: Allergic sensitization is associated with extensive tonsillar transcriptomic alterations and changes in immune related genes and pathways. Distinct differences were found between aero-allergen and food-allergen sensitization

Tonsillar transcriptional profiles in atopic and non-atopic subjects

Abstract Background: Emerging research suggests that local lymphatic tissue such as tonsils have important role in regulating the immune responses. However, allergen sensitization-induced alterations in transcriptome of tonsils are not known. Objectives: To examine the key differences in tonsillar gene expression between atopic and non-atopic subjects and further by type of sensitization. Methods: RNA-sequencing was performed on 52 tonsillar samples from atopic and non-atopic tonsillectomy patients. Sensitization to common food- and aero-allergen was defined by allergen specific IgE. Following groups were studied: (1) aero- and foodallergen sensitized (AS+FS) versus non-sensitized (NS), (2) aeroallergen-sensitized (AS) versus food-allergen sensitized (FS), (3) AS versus NS, (4) FS versus NS. Bioinformatics analysis was done using DESeq2(v3.10.2), WGCNA and GATK pipeline in R software (v3.3.1). Protein–protein interaction network was made from String database. Results: We studied 13 aeroallergen-sensitized, 6 food-allergen sensitized, 4 both food-and aero-allergen-sensitized and 29 non-sensitized tonsillectomy patients. Overall, 697 unique differentially expressed genes (DEGs) were detected in all sensitized subgroups including chemokines (CXCL2, CXCL8, CXCL10, CXCL11), IL-20RA,MUC1 and MUC20. When comparing different groups, the gene expression profiles overlapped except the AS versus FS group comparison, suggesting significantly different gene expression between the two sensitization subgroups. Furthermore, aeroallergen-sensitized subjects had more prominent immune responses compared with non-sensitized and food-allergen sensitized subjects including gene expression for IL-17 pathway and Toll-like receptor signalling pathway. Conclusion: Allergic sensitization is associated with extensive tonsillar transcriptomic alterations and changes in immune related genes and pathways. Distinct differences were found between aero-allergen and food-allergen sensitization. KEYWORDS aeroallergen, atopy, IL-17, tonsil, transcriptomePeer reviewe

Rhinovirus species and tonsillar immune responses

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-alpha, IFN-beta, IFN-gamma, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-beta, 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-alpha (P = 0.045) and decreased RORC2 expression (P = 0.025). Conclusions Rhinovirus species associated differently with clinical characteristics and tonsillar cytokine responses.Peer reviewe

Intratonsillar detection of 27 distinct viruses: A cross-sectional study

Palatine tonsils have been observed to harbor several distinct respiratory and herpesviruses in separate studies. In this study, the presence of these viruses in palatine tonsils was comprehensively studied in both children and adults. A cross-sectional analysis of 181 patients (median age 22 years; range, 2.6-66) operated for a benign tonsillar disease was conducted. Real-time polymerase chain reaction was performed to detect 27 distinct viruses in all: eight human herpesviruses, 16 respiratory viruses, parvo B19, and polyoma BK/JC viruses. Clinical characteristics of the patients and underlying conditions were evaluated. In total, 92% of patients had virus detected in tonsils (Epstein-Barr virus 72%, human herpesvirus 7, and 6B 54% and 16%, respectively, enterovirus 18%, parvovirus B19 7% and the rest <4%). No herpes simplex virus 2, varicella zoster virus, polyoma JC virus, parainfluenza-, metapneumo-, or coronaviruses were found. Enterovirus was more common in children and was frequently observed in the presence of HHV6B. None of the viruses showed a positive association to the tonsillar disease. Respiratory symptoms were not associated with the prevalence of viruses. This study comprehensively reports a cross-sectional view of intratonsillar virus infections in elective tonsillectomy patients in a wide age range cohort. Tonsils are a major virus reservoir for distinct herpes and respiratory viruses without a positive association with tonsillar disease or respiratory symptoms

Herpesvirus infections in adenoids in patients with chronic adenotonsillar disease

Adenoids and tonsils have gained interest as a new in vivo model to study local immune functions and virus reservoirs. Especially herpesviruses are interesting because their prevalence and persistence in local lymphoid tissue are incompletely known. Our aim was to study herpesvirus and common respiratory virus infections in nonacutely ill adenotonsillar surgery patients. Adenoid and/or palatine tonsil tissue and nasopharyngeal aspirate (NPA) samples were collected from elective adenoidectomy (n = 45) and adenotonsillectomy (n = 44) patients (median age: 5, range: 1-20). Real-time polymerase chain reaction was used to detect 22 distinct viruses from collected samples. The overall prevalence of herpesviruses was 89% and respiratory viruses 94%. Human herpesviruses 6 (HHV6), 7 (HHV7), and Epstein-Barr virus (EBV) were found, respectively, in adenoids (33%, 26%, 25%), tonsils (45%, 52%, 23%), and NPA (46%, 38%, 25%). Copy numbers of the HHV6 and HHV7 genome were significantly higher in tonsils than in adenoids. Patients with intra-adenoid HHV6 were younger than those without. Detection rates of EBV and HHV7 showed agreement between corresponding sample types. This study shows that adenoid and tonsil tissues commonly harbor human herpes- and respiratory viruses, and it shows the differences in virus findings between sample types

Insect herbivory dampens Subarctic birch forest C sink response to warming

Climate warming is anticipated to make high latitude ecosystems stronger C sinks through increasing plant production. This effect might, however, be dampened by insect herbivores whose damage to plants at their background, non-outbreak densities may more than double under climate warming. Here, using an open-air warming experiment among Subarctic birch forest field layer vegetation, supplemented with birch plantlets, we show that a 2.3 degrees C air and 1.2 degrees C soil temperature increase can advance the growing season by 1-4 days, enhance soil N availability, leaf chlorophyll concentrations and plant growth up to 400%, 160% and 50% respectively, and lead up to 122% greater ecosystem CO2 uptake potential. However, comparable positive effects are also found when insect herbivory is reduced, and the effect of warming on C sink potential is intensified under reduced herbivory. Our results confirm the expected warming-induced increase in high latitude plant growth and CO2 uptake, but also reveal that herbivorous insects may significantly dampen the strengthening of the CO2 sink under climate warming. Warming is expected to increase C sink capacity in high-latitude ecosystems, but plant-herbivore interactions could moderate or offset this effect. Here, Silfver and colleagues test individual and interactive effects of warming and insect herbivory in a field experiment in Subarctic forest, showing that even low intensity insect herbivory strongly reduces C sink potential

Tonsillar transcriptional profiles in atopic and non-atopic subjects

Background Emerging research suggests that local lymphatic tissue such as tonsils have important role in regulating the immune responses. However, allergen sensitization-induced alterations in transcriptome of tonsils are not known. Objectives To examine the key differences in tonsillar gene expression between atopic and non-atopic subjects and further by type of sensitization. Methods RNA-sequencing was performed on 52 tonsillar samples from atopic and non-atopic tonsillectomy patients. Sensitization to common food- and aero-allergen was defined by allergen specific IgE. Following groups were studied: (1) aero- and food-allergen sensitized (AS+FS) versus non-sensitized (NS), (2) aeroallergen-sensitized (AS) versus food-allergen sensitized (FS), (3) AS versus NS, (4) FS versus NS. Bioinformatics analysis was done using DESeq2(v3.10.2), WGCNA and GATK pipeline in R software (v3.3.1). Protein-protein interaction network was made from String database. Results We studied 13 aeroallergen-sensitized, 6 food-allergen sensitized, 4 both food-and aero-allergen-sensitized and 29 non-sensitized tonsillectomy patients. Overall, 697 unique differentially expressed genes (DEGs) were detected in all sensitized subgroups including chemokines (CXCL2, CXCL8, CXCL10, CXCL11), IL-20RA, MUC1 and MUC20. When comparing different groups, the gene expression profiles overlapped except the AS versus FS group comparison, suggesting significantly different gene expression between the two sensitization subgroups. Furthermore, aeroallergen-sensitized subjects had more prominent immune responses compared with non-sensitized and food-allergen sensitized subjects including gene expression for IL-17 pathway and Toll-like receptor signalling pathway. Conclusion Allergic sensitization is associated with extensive tonsillar transcriptomic alterations and changes in immune related genes and pathways. Distinct differences were found between aero-allergen and food-allergen sensitization.</p

Effects of experimental warming on Betula nana epidermal cell growth tested over its maximum climatological growth range

Numerous long-term, free-air plant growth facilities currently explore vegetation responses to the ongoing climate change in northern latitudes. Open top chamber (OTC) experiments as well as the experimental set-ups with active warming focus on many facets of plant growth and performance, but information on morphological alterations of plant cells is still scarce. Here we compare the effects of in-situ warming on leaf epidermal cell expansion in dwarf birch, Betula nana in Finland, Greenland, and Poland. The localities of the three in-situ warming experiments represent contrasting regions of B. nana distribution, with the sites in Finland and Greenland representing the current main distribution in low and high Arctic, respectively, and the continental site in Poland as a B. nana relict Holocene microrefugium. We quantified the epidermal cell lateral expansion by microscopic analysis of B. nana leaf cuticles. The leaves were produced in paired experimental treatment plots with either artificial warming or ambient temperature. At all localities, the leaves were collected in two years at the end of the growing season to facilitate between-site and within-site comparison. The measured parameters included the epidermal cell area and circumference, and using these, the degree of cell wall undulation was calculated as an Undulation Index (UI). We found enhanced leaf epidermal cell expansion under experimental warming, except for the extremely low temperature Greenland site where no significant difference occurred between the treatments. These results demonstrate a strong response of leaf growth at individual cell level to growing season temperature, but also suggest that in harsh conditions other environmental factors may limit this response. Our results provide evidence of the relevance of climate warming for plant leaf maturation and underpin the importance of studies covering large geographical scales.</p

Persistent human bocavirus 1 infection and tonsillar immune responses

Background Persistent human bocavirus 1 (HBoV1) infection is a common finding in patients suffering from chronic tonsillar disease. However, the associations between HBoV1 infection and specific immune reactions are not completely known. We aimed to compare in vivo expression of T-cell cytokines, transcription factors, and type I/III interferons in human tonsils between HBoV1-positive and -negative tonsillectomy patients. Methods Tonsil tissue samples, nasopharyngeal aspirate (NPA), and serum samples were obtained from 143 immunocompetent adult and child tonsillectomy patients. HBoV1 and 14 other respiratory viruses were detected in NPAs and tonsil tissues by polymerase chain reaction (PCR). Serology and semi-quantitative PCR were used for diagnosing HBoV1 infections. Expression of 14 cytokines and transcription factors (IFN-alpha, IFN-beta, IFN-gamma, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-beta, FOXP3, GATA3, RORC2, Tbet) was analyzed by quantitative reverse-transcription (RT)-PCR in tonsil tissues. Results HBoV1 was detected by PCR in NPA and tonsils from 25 (17%) study patients. Serology results indicated prior nonacute infections in 81% of cases. Tonsillar cytokine responses were affected by HBoV1 infection. The suppression of two transcription factors, RORC2 and FOXP3, was associated with HBoV1 infection (p Conclusions Our study shows distinctively decreased T-helper(17) and T-regulatory type immune responses in local lymphoid tissue in HBoV1-positive tonsillectomy patients. HBoV1 may act as a suppressive immune modulator.</p