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1.
Int J Mol Sci ; 22(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33947066

RESUMO

The pathogenesis of nasal inflammatory diseases is related to various factors such as anatomical structure, heredity, and environment. The nasal microbiota play a key role in coordinating immune system functions. Dysfunction of the microbiota has a significant impact on the occurrence and development of nasal inflammation. This review will introduce the positive and negative roles of microbiota involved in immunity surrounding nasal mucosal diseases such as chronic sinusitis and allergic rhinitis. In addition, we will also introduce recent developments in DNA sequencing, metabolomics, and proteomics combined with computation-based bioinformatics.


Assuntos
Microbiota , Cavidade Nasal/microbiologia , Mucosa Nasal/microbiologia , Rinite/microbiologia , Sinusite/microbiologia , Adulto , Antígenos de Bactérias/imunologia , Criança , Doença Crônica , Disbiose/imunologia , Disbiose/microbiologia , Humanos , Metabolômica/métodos , Cavidade Nasal/imunologia , Mucosa Nasal/imunologia , Proteômica/métodos , Rinite/imunologia , Rinite Alérgica/imunologia , Rinite Alérgica/microbiologia , Análise de Sequência de DNA/métodos , Sinusite/imunologia
2.
Anat Rec (Hoboken) ; 304(6): 1185-1193, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33856123

RESUMO

Estrogen is an important hormone for health in both genders. It is indispensable to glucose homeostasis, immune robustness, bone health, cardiovascular health, and neural functions. The main way that estrogen acts in the cells is through estrogen receptors (ERs). The presence of specific estrogen receptors is required for estrogen to have its characteristic ubiquitous action in almost all tissues. Estrogen receptor alpha (ERα) and estrogen receptor beta (ERß) are the major isoforms of estrogen that are highly specific in humans and enable selective hormonal actions in different tissues. This article reviews some of the observed estrogen actions and effects in different tissues and cells through these specific receptors. This ubiquitous, almost ordinary hormone may reveal itself as a significant factor that helped us to better understand the complexity of the human immune system response against respiratory infections, including the COVID-19, and especially in the current state of this painful pandemic.


Assuntos
59585/imunologia , Receptor alfa de Estrogênio/imunologia , Receptor beta de Estrogênio/imunologia , Sistema Imunitário/imunologia , Sistema Respiratório/imunologia , 59565/imunologia , Animais , 59585/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Humanos , Sistema Imunitário/metabolismo , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Sistema Respiratório/metabolismo , 59565/metabolismo
3.
JCI Insight ; 6(9)2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33822777

RESUMO

BACKGROUNDCoronavirus disease 2019 (COVID-19) is more benign in children compared with adults for unknown reasons. This contrasts with other respiratory viruses where disease manifestations are often more severe in children. We hypothesize that a more robust early innate immune response to SARS coronavirus 2 (SARS-CoV-2) protects against severe disease.METHODSClinical outcomes, SARS-CoV-2 viral copies, and cellular gene expression were compared in nasopharyngeal swabs obtained at the time of presentation to the emergency department from 12 children and 27 adults using bulk RNA sequencing and quantitative reverse-transcription PCR. Total protein, cytokines, and anti-SARS-CoV-2 IgG and IgA were quantified in nasal fluid.RESULTSSARS-CoV-2 copies, angiotensin-converting enzyme 2, and TMPRSS2 gene expression were similar in children and adults, but children displayed higher expression of genes associated with IFN signaling, NLRP3 inflammasome, and other innate pathways. Higher levels of IFN-α2, IFN-γ, IP-10, IL-8, and IL-1ß protein were detected in nasal fluid in children versus adults. Children also expressed higher levels of genes associated with immune cells, whereas expression of those associated with epithelial cells did not differ in children versus adults. Anti-SARS-CoV-2 IgA and IgG were detected at similar levels in nasal fluid from both groups. None of the children required supplemental oxygen, whereas 7 adults did (P = 0.03); 4 adults died.CONCLUSIONThese findings provide direct evidence of a more vigorous early mucosal immune response in children compared with adults and suggest that this contributes to favorable clinical outcomes.FUNDINGNIH grants R01 AI134367, UL1 TR002556, T32 AI007501, T32GM007288, P30 AI124414; an Albert Einstein College of Medicine Dean's COVID-19 Pilot Research Award; and the Eric J. Heyer, MD, PhD Translational Research Pilot Project Award.


Assuntos
/imunologia , Imunidade nas Mucosas , Adulto , Idoso , Anticorpos Antivirais/metabolismo , Criança , Pré-Escolar , Citocinas/metabolismo , Feminino , Humanos , Imunidade Inata/genética , Imunidade nas Mucosas/genética , Lactente , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/imunologia , Pandemias , Transcriptoma
4.
mBio ; 12(2)2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33906927

RESUMO

SARS-CoV-2 infection causing the COVID-19 pandemic calls for immediate interventions to avoid viral transmission, disease progression, and subsequent excessive inflammation and tissue destruction. Primary normal human bronchial epithelial cells are among the first targets of SARS-CoV-2 infection. Here, we show that ColdZyme medical device mouth spray efficiently protected against virus entry, excessive inflammation, and tissue damage. Applying ColdZyme to fully differentiated, polarized human epithelium cultured at an air-liquid interphase (ALI) completely blocked binding of SARS-CoV-2 and increased local complement activation mediated by the virus as well as productive infection of the tissue model. While SARS-CoV-2 infection resulted in exaggerated intracellular complement activation immediately following infection and a drop in transepithelial resistance, these parameters were bypassed by single pretreatment of the tissues with ColdZyme mouth spray. Crucially, our study highlights the importance of testing already evaluated and safe drugs such as ColdZyme mouth spray for maintaining epithelial integrity and hindering SARS-CoV-2 entry within standardized three-dimensional (3D) in vitro models mimicking the in vivo human airway epithelium.IMPORTANCE Although our understanding of COVID-19 continuously progresses, essential questions regarding prophylaxis and treatment remain open. A hallmark of severe SARS-CoV-2 infection is a hitherto-undescribed mechanism leading to excessive inflammation and tissue destruction associated with enhanced pathogenicity and mortality. To tackle the problem at the source, transfer of SARS-CoV-2, subsequent binding, infection, and inflammatory responses have to be avoided. In this study, we used fully differentiated, mucus-producing, and ciliated human airway epithelial cultures to test the efficacy of ColdZyme medical device mouth spray in terms of protection from SARS-CoV-2 infection. Importantly, we found that pretreatment of the in vitro airway cultures using ColdZyme mouth spray resulted in significantly shielding the epithelial integrity, hindering virus binding and infection, and blocking excessive intrinsic complement activation within the airway cultures. Our in vitro data suggest that ColdZyme mouth spray may have an impact in prevention of COVID-19.


Assuntos
Antivirais/farmacologia , Mucosa Respiratória/efeitos dos fármacos , /efeitos dos fármacos , Brônquios/citologia , /virologia , Complemento C3/imunologia , Células Epiteliais , Humanos , Imunidade Inata/efeitos dos fármacos , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/imunologia , Mucosa Nasal/virologia , Sprays Orais , Mucosa Respiratória/imunologia , Mucosa Respiratória/virologia , Ligação Viral/efeitos dos fármacos
5.
Arch Biochem Biophys ; 702: 108828, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33741336

RESUMO

Eosinophils (Eos) are the canonical effector cells in allergic rhinitis (AR) and many inflammatory diseases. The mechanism of eosinophilia occurring in the lesion sites is not fully understood yet. Twist1 protein (Twist, in short) is an apoptosis inhibitor that also has immune regulatory functions. This study aims to investigate the role of Twist in the pathogenesis of eosinophilia in AR. In this study, surgically removed human nasal mucosal samples were obtained from patients with chronic sinusitis and nasal polyps with AR (the AR group) or without AR (the nAR group). Eos were isolated from the samples by flow cytometry. We found that abundant Eos were obtained from the surgically removed nasal mucosa tissues of both nAR and AR groups. Significantly higher Ras activation was detected in AR Eos than that in nAR Eos. Ras activation was associated with the apoptosis resistance in AR Eos. The Twist (an apoptosis inhibitor) expression was higher in AR Eos, which was positively correlated with the Ras activation status. The sensitization to IgG induced Twist expression in Eos, in which Ras activated the MAPK-HIF-1α pathway, the latter promoted the Twist gene transcription. Twist bound Rac GTPase activating protein-1 to sustain the Ras activation in Eos. Ras activation sustained the apoptosis resistance in Eos. In conclusion, high Ras activation was detected in the AR nasal mucosal tissue-isolated Eos. IgG-sensitization induced Ras activation and Twist expression in Eos, that conferred Eos the apoptosis resistance.


Assuntos
Apoptose , Eosinófilos/citologia , Mucosa Nasal/imunologia , Rinite Alérgica/metabolismo , Rinite Alérgica/patologia , Proteína 1 Relacionada a Twist/metabolismo , Adulto , Feminino , Proteínas Ativadoras de GTPase/metabolismo , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Rinite Alérgica/imunologia , Adulto Jovem , Proteínas ras/metabolismo
6.
Front Immunol ; 12: 595343, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717074

RESUMO

Likely as in other viral respiratory diseases, SARS-CoV-2 elicit a local immune response, which includes production and releasing of both cytokines and secretory immunoglobulin (SIgA). Therefore, in this study, we investigated the levels of specific-SIgA for SARS-CoV-2 and cytokines in the airways mucosa 37 patients who were suspected of COVID-19. According to the RT-PCR results, the patients were separated into three groups: negative for COVID-19 and other viruses (NEGS, n = 5); negative for COVID-19 but positive for the presence of other viruses (OTHERS, n = 5); and the positive for COVID-19 (COVID-19, n = 27). Higher specific-SIgA for SARS-CoV-2, IFN-ß, and IFN-γ were found in the COVID-19 group than in the other groups. Increased IL-12p70 levels were observed in OTHERS group as compared to COVID-19 group. When the COVID-19 group was sub stratified according to the illness severity, significant differences and correlations were found for the same parameters described above comparing severe COVID-19 to the mild COVID-19 group and other non-COVID-19 groups. For the first time, significant differences are shown in the airway's mucosa immune responses in different groups of patients with or without respiratory SARS-CoV-2 infection.


Assuntos
Anticorpos Antivirais/metabolismo , Imunoglobulina A/metabolismo , Interferons/metabolismo , Pulmão/patologia , Mucosa Nasal/metabolismo , /fisiologia , Adolescente , Adulto , Idoso , Brasil , Criança , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/imunologia , Adulto Jovem
7.
Int Immunopharmacol ; 93: 107406, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33601246

RESUMO

In patients with COVID-19,type 2 diabetes mellitus (T2DM) can impair the function of nasal-associated lymphoid tissue (NALT) and result in olfactory dysfunction. Exploring the causative alterations of T2DM within the nasal mucosa and NALT could provide insight into the pathogenic mechanisms and bridge the gap between innate immunity and adaptive immunity for virus clearance. Here, we designed a case-control study to compare the olfactory function (OF) among the groups of normal control (NC), COVID-19 mild pneumonia (MP), and MP patients with T2DM (MPT) after a 6-8 months' recovery, in which MPT had a higher risk of hyposmia than MP and NC. No significant difference was found between the MP and NC. This elevated risk of hyposmia indicated that T2DM increased COVID-19 susceptibility in the nasal cavity with unknown causations. Therefore, we used the T2DM animal model (db/db mice) to evaluate how T2DM increased COVID-19 associated susceptibilities in the nasal mucosa and lymphoid tissues. Db/db mice demonstratedupregulated microvasculature ACE2 expression and significant alterations in lymphocytes component of NALT. Specifically, db/db mice NALT had increased immune-suppressive TCRγδ+ CD4-CD8- T and decreased immune-effective CD4+/CD8+ TCRß+ T cells and decreased mucosa-protective CD19+ B cells. These results indicated that T2DM could dampen the first-line defense of nasal immunity, and further mechanic studies of metabolic damage and NALT restoration should be one of the highest importance for COVID-19 healing.


Assuntos
/imunologia , /imunologia , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/virologia , Adulto , Animais , Linfócitos B/imunologia , /fisiopatologia , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Imunidade nas Mucosas/imunologia , Tecido Linfoide/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Modelos Animais , Mucosa Nasal/imunologia , Mucosa Olfatória/metabolismo , Fatores de Risco , Serina Endopeptidases/metabolismo , Linfócitos T/imunologia
8.
Int Immunopharmacol ; 93: 107400, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33529911

RESUMO

RGFP966 is a selective inhibitor of histone deacetylase 3 (HDAC3) playing crucial roles in triggering allergic and inflammatory responses. Whereas, its role in allergic rhinitis (AR) remains uncertain. This study sought to illustrate the role and mechanism of HDAC3 inhibitor RGFP966 on allergic and inflammatory responses in murine AR. RGFP966 administration was applied on murine AR. HE staining, PAS staining, toluidine blue staining, immunohistochemistry staining and real-time PCR methods were used to assess eosinophils, goblet cells, mast cells, HDAC3 positive cells and mRNA levels in nasal tissues of mice. HDAC3 activities in nasal tissues were quantified with HDAC3 Activity Assay Kit. We collected blood and nasal lavage fluid (NLF) of mice for assaying IgE, inflammatory cytokines and inflammatory cells. Results indicated that RGFP966 intervention attenuated sneezing, nose rubbing, IgE, inflammatory cytokines, eosinophils, goblet cells, mast cells, inflammatory cells, HDAC3 levles and activities in RGFP966 treated mice. In conclusion, RGFP966 might reduce HDAC3 expression and HDAC3 activities, and then eosinophils and mast cells recruitment, goblet cells proliferation and inflammatory cytokines levels are decreased, resulting in the alleviation of allergic and inflammatory responses in AR mice.


Assuntos
Acrilamidas/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Hipersensibilidade/tratamento farmacológico , Inflamação/tratamento farmacológico , Mucosa Nasal/imunologia , Fenilenodiaminas/uso terapêutico , Alérgenos/imunologia , Animais , Modelos Animais de Doenças , Feminino , Histona Desacetilases/metabolismo , Humanos , Imunoglobulina E/sangue , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia
9.
Int Immunopharmacol ; 91: 107306, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33383443

RESUMO

The brain has special importance and is known as immune privileged site to and from which trafficking of immune cells is tightly regulated. However, in Alzheimer's disease (AD) the balance of the immune system is disturbed and damages the brain. Given the anatomical and immunological barriers in the brain, we attempted to evaluate if the neuroinflammation occurred in AD is limited to the brain or is expanded to the periphery. Hence, rat model of AD was induced by intra-hippocampal injection of beta-amyloid1-42. Then, nasal, brain, cervical lymph nodes, and spleen were isolated. Then, profile of T-helper (Th)1, Th2, and Th17, represented by IFN-γ, IL-4, and IL-17, respectively, was determined. The results were compared between the organs and with the corresponding tissue in normal animals. IFN-γ and IL-17 levels in the brain, nasal tissue, and cervical lymph nodes of AD model were higher than IL-4, comparing with normal animals. Similar profile was observed in the spleen. The results suggest Alzheimer's as a systemic disease whose complication are observed locally. The possibility of epitope spreading and autoimmune nature of AD is raised again. Interestingly, although AD model was induced by injection of beta-amyloid in the brain, the cellular responses in the brain and nasal tissue were similar indicating that the nasal-brain axis is two-sided. In addition, both of IFN-γ/IL-17 and IL-4/IL-17 ratios, just in nasal tissue were markedly decreased in AD model comparing with normal animals. This suggests development of future nasal-based diagnostic approaches.


Assuntos
Doença de Alzheimer/imunologia , Encéfalo/imunologia , Linfonodos/imunologia , Mucosa Nasal/imunologia , Baço/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides , Animais , Comportamento Animal , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Citocinas/metabolismo , Modelos Animais de Doenças , Linfonodos/metabolismo , Masculino , Mucosa Nasal/metabolismo , Fragmentos de Peptídeos , Fenótipo , Ratos Sprague-Dawley , Baço/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Células Th2/imunologia , Células Th2/metabolismo
10.
Science ; 370(6513)2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33033192

RESUMO

The variable outcome of viral exposure is only partially explained by known factors. We administered respiratory syncytial virus (RSV) to 58 volunteers, of whom 57% became infected. Mucosal neutrophil activation before exposure was highly predictive of symptomatic RSV disease. This was associated with a rapid, presymptomatic decline in mucosal interleukin-17A (IL-17A) and other mediators. Conversely, those who resisted infection showed presymptomatic activation of IL-17- and tumor necrosis factor-related pathways. Vulnerability to infection was not associated with baseline microbiome but was reproduced in mice by preinfection chemokine-driven airway recruitment of neutrophils, which caused enhanced disease mediated by pulmonary CD8+ T cell infiltration. Thus, mucosal neutrophilic inflammation at the time of RSV exposure enhances susceptibility, revealing dynamic, time-dependent local immune responses before symptom onset and explaining the as-yet unpredictable outcomes of pathogen exposure.


Assuntos
Mucosa Nasal/imunologia , Mucosa Nasal/virologia , Ativação de Neutrófilo , Neutrófilos/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sinciciais Respiratórios , Adolescente , Adulto , Animais , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Quimiocina CXCL1/farmacologia , Humanos , Inflamação/imunologia , Inflamação/virologia , Interleucina-17/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Neutrófilos/efeitos dos fármacos , Infecções por Vírus Respiratório Sincicial/patologia , Fator de Necrose Tumoral alfa/imunologia , Adulto Jovem
12.
Am J Respir Cell Mol Biol ; 63(5): 707-709, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32857620
14.
Cell ; 181(5): 1016-1035.e19, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32413319

RESUMO

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discovered that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.


Assuntos
Células Epiteliais Alveolares/metabolismo , Enterócitos/metabolismo , Células Caliciformes/metabolismo , Interferon Tipo I/metabolismo , Mucosa Nasal/citologia , Peptidil Dipeptidase A/genética , Adolescente , Células Epiteliais Alveolares/imunologia , Animais , Betacoronavirus/fisiologia , Linhagem Celular , Células Cultivadas , Criança , Infecções por Coronavirus/virologia , Enterócitos/imunologia , Células Caliciformes/imunologia , Infecções por HIV/imunologia , Humanos , Influenza Humana/imunologia , Interferon Tipo I/imunologia , Pulmão/citologia , Pulmão/patologia , Macaca mulatta , Camundongos , Mycobacterium tuberculosis , Mucosa Nasal/imunologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/virologia , Receptores Virais/genética , Serina Endopeptidases/metabolismo , Análise de Célula Única , Tuberculose/imunologia , Regulação para Cima
15.
Int Arch Allergy Immunol ; 181(5): 385-394, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32259823

RESUMO

BACKGROUND: Drug-free viscous nasal applications have been shown to reduce nasal symptoms in individuals with seasonal allergic rhinitis (SAR). Nascum®-Plus (NP), a commercially available thixotropic gel, has been designed to reduce dryness and soreness of the nasal mucosa and prevent the absorption of small particles. OBJECTIVES: The aim of this study was to assess the efficacy of single-dose NP in treating nasal symptoms and secretion during challenge in an allergen challenge chamber (ACC). Furthermore, the effect of this treatment on biomarkers and immune cells of the allergic cascade were measured. METHODS: This open-label, cross-over, sequence-randomized, monocentric trial randomized 18 adults with SAR and a positive skin prick test reaction to Dactylis glomerata pollen to receive NP or no treatment during two 4-h ACC sessions 3 weeks apart. On Day 1, 9 subjects were challenged for 4 h with treatment, the other 9 without treatment, and vice versa on Day 22. Nasal lavage fluid and nasal filter eluate samples were obtained pre, 2, and 18 h post challenge in the ACC. RESULTS: NP significantly reduced nasal symptoms, assessed by total nasal symptom score (p < 0.001), and minimized nasal secretion (p = 0.047), while no significant effect on biomarkers and immune cells in the nasal fluid was observed. The treatment was safe and well-tolerated. CONCLUSIONS: The physical barrier built by NP nasal gel can be safely applied in patients with allergic rhinitis. It reduces allergic nasal symptoms and secretion, but application of a single dose does not affect local inflammatory biomarkers.


Assuntos
Óleo de Rícino/administração & dosagem , Mucosa Nasal/efeitos dos fármacos , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/prevenção & controle , Dióxido de Silício/administração & dosagem , Administração Intranasal , Adulto , Biomarcadores , Coloides , Feminino , Géis , Humanos , Inflamação/imunologia , Inflamação/prevenção & controle , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/imunologia
16.
J Allergy Clin Immunol ; 145(3): 740-750, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32145873

RESUMO

Chronic rhinosinusitis (CRS) is one of the most common chronic diseases worldwide. It is a heterogeneous disease, and geographical or ethnic differences in inflammatory pattern in nasal mucosa are major issues. Tissue eosinophilia in CRS is highly associated with extensive sinus disease, recalcitrance, and a higher nasal polyp (NP) recurrence rate after surgery. The prevalence of eosinophilic CRS (ECRS) is increasing in Asian countries within the last 2 decades, and this trend appears to be occurring across the world. International consensus criteria for ECRS are required for the accurate understanding of disease pathology and precision medicine. In a multicenter large-scale epidemiological survey, the "Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis study," ECRS was definitively defined when the eosinophil count in nasal mucosa is greater than or equal to 70 eosinophils/hpf (magnification, ×400), and this study proposed an algorithm that classifies CRS into 4 groups according to disease severity. The main therapeutic goal with ECRS is to eliminate or diminish the bulk of NP tissue. NPs are unique abnormal lesions that grow from the lining of the nasal and paranasal sinuses, and type 2 inflammation plays a critical role in NP development in patients with ECRS. An imbalance between protease and endogenous protease inhibitors might play a pivotal role in the initiation and exacerbation of type 2 inflammation in ECRS. Intraepithelial mast cells in NPs, showing a tryptase+, chymase- phenotype, may also enhance type 2 inflammation. Intense edema and reduced fibrosis are important histological features of eosinophilic NPs. Mucosal edema mainly consists of exuded plasma protein, and excessive fibrin deposition would be expected to contribute to the retention of proteins from capillaries and thereby perpetuate mucosal edema that may play an etiological role in NPs. Upregulation of the coagulation cascade and downregulation of fibrinolysis strongly induce abnormal fibrin deposition in nasal mucosa, and type 2 inflammation plays a central role in the imbalance of coagulation and fibrinolysis.


Assuntos
Fibrina/metabolismo , Inflamação/imunologia , Inflamação/patologia , Pólipos Nasais/imunologia , Pólipos Nasais/patologia , Doença Crônica , Eosinófilos/imunologia , Eosinófilos/patologia , Humanos , Imunidade Inata/imunologia , Inflamação/metabolismo , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Pólipos Nasais/metabolismo , Rinite/imunologia , Rinite/metabolismo , Rinite/patologia , Sinusite/imunologia , Sinusite/metabolismo , Sinusite/patologia
17.
Vet Res ; 51(1): 21, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093748

RESUMO

Sialoadhesin (Sn) and CD163 have been recognized as two important mediators for porcine reproductive and respiratory syndrome virus (PRRSV) in host macrophages. Recently, it has been demonstrated that the highly virulent Lena strain has a wider macrophage tropism than the low virulent LV strain in the nasal mucosa. Not only CD163+Sn+ macrophages are infected by Lena but also CD163+Sn- macrophages. This suggests that an alternative receptor exists for binding and internalization of PRRSV Lena in the CD163+Sn- macrophages. Further investigation to find the new entry receptor was hampered by the difficulty of isolating these macrophages from the nasal mucosa. In the present study, a new population of CD163+Sn- cells has been identified that is specifically localized in the nasal lamina propria and can be isolated by an intranasal digestion approach. Isolated nasal cells were characterized using specific cell markers and their susceptibility to two different PRRSV-1 strains (LV and Lena) was tested. Upon digestion, 3.2% (flow cytometry)-6.4% (confocal microscopy) of the nasal cells were identified as CD163+ and all (99.7%) of these CD163+ cells were Sn-. These CD163+Sn- cells, designated as "nasal surface macrophages", showed a 4.9 times higher susceptibility to the Lena strain than to the LV strain. Furthermore, the Lena-inoculated cell cultures showed an upregulation of CD163. These results showed that our new cell isolation system is ideal for the further functional and phenotypical analysis of the new population of nasal surface macrophages and further research on the molecular pathogenesis of PRRSV in the nose.


Assuntos
Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/imunologia , Macrófagos/imunologia , Síndrome Respiratória e Reprodutiva Suína/imunologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/fisiologia , Receptores de Superfície Celular/imunologia , Animais , Técnicas de Cultura de Células , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/imunologia , Suínos
18.
Infect Immun ; 88(5)2020 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-32094254

RESUMO

Localized skin lesions are characteristic of cutaneous leishmaniasis (CL); however, Leishmania (Viannia) species, which are responsible for most CL cases in the Americas, can spread systemically, sometimes resulting in mucosal disease. Detection of Leishmania has been documented in healthy mucosal tissues (conjunctiva, tonsils, and nasal mucosa) and healthy skin of CL patients and in individuals with asymptomatic infection in areas of endemicity of L (V) panamensis and L (V) braziliensis transmission. However, the conditions and mechanisms that favor parasite persistence in healthy mucosal tissues are unknown. In this descriptive study, we compared the cell populations of the nasal mucosa (NM) of healthy donors and patients with active CL and explored the immune gene expression signatures related to molecular detection of Leishmania in this tissue in the absence of clinical signs or symptoms of mucosal disease. The cellular composition and gene expression profiles of NM samples from active CL patients were similar to those of healthy volunteers, with a predominance of epithelial over immune cells, and within the CD45+ cell population, a higher frequency of CD66b+ followed by CD14+ and CD3+ cells. In CL patients with molecular evidence of Leishmania persistence in the NM, genes characteristic of an anti-inflammatory and tissue repair responses (IL4R, IL5RA, POSTN, and SATB1) were overexpressed relative to NM samples from CL patients in which Leishmania was not detected. Here, we report the first immunological description of subclinically infected NM tissues of CL patients and provide evidence of a local anti-inflammatory environment favoring parasite persistence in the NM.


Assuntos
Leishmaniose Cutânea/imunologia , Mucosa Nasal/imunologia , Adulto , Antígenos CD/imunologia , Moléculas de Adesão Celular/imunologia , Feminino , Humanos , Subunidade alfa de Receptor de Interleucina-4/imunologia , Subunidade alfa de Receptor de Interleucina-5/imunologia , Leishmania/imunologia , Masculino , Proteínas de Ligação à Região de Interação com a Matriz/imunologia , Pele/imunologia , Transcriptoma/imunologia
19.
PLoS One ; 15(2): e0228463, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32027689

RESUMO

Infection with Brucella abortus causes contagious zoonosis, brucellosis, and leads to abortion in animals and chronic illness in humans. Chitosan nanoparticles (CNs), biocompatible and nontoxic polymers, acts as a mucosal adjuvant. In our previous study, B. abortus malate dehydrogenase (Mdh) was loaded in CNs, and it induced high production of pro-inflammatory cytokines in THP-1 cells and systemic IgA in BALB/C mice. In this study, the time-series gene expression analysis of nasal-associated lymphoid tissue (NALT) was performed to identify the mechanism by which Mdh affect the target site of nasal immunization. We showed that intranasal immunization of CNs-Mdh reduced cell viability of epithelial cells and muscle cells at first 1 h, then induced cellular movement of immune cells such as granulocytes, neutrophils and lymphocytes at 6h, and activated IL-6 signaling pathway at 12h within NALT. These activation of immune cells also promoted signaling pathway for high-mobility group box 1 protein (HMGB1), followed by the maturation of DCs required for mucosal immunity. The CNs also triggered the response to other organism and inflammatory response, showing it is immune-enhancing adjuvant. The ELISA showed that significant production of specific IgA was detected in the fecal excretions and genital secretions from the CNs-Mdh-immunized group after 2 weeks-post immunization. Collectively, these results suggest that B. abortus Mdh-loaded CNs triggers activation of HMGB1, IL-6 and DCs maturation signaling within NALT and induce production of systemic IgG and IgA.


Assuntos
Formação de Anticorpos/fisiologia , Brucella abortus/imunologia , Brucelose/prevenção & controle , Imunização/métodos , Tecido Linfoide/imunologia , Malato Desidrogenase/imunologia , Administração Intranasal , Animais , Formação de Anticorpos/efeitos dos fármacos , Brucella abortus/metabolismo , Brucelose/imunologia , Quitosana/administração & dosagem , Quitosana/química , Quitosana/imunologia , Quitosana/farmacologia , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Feminino , Imunidade nas Mucosas/efeitos dos fármacos , Imunogenicidade da Vacina , Tecido Linfoide/efeitos dos fármacos , Malato Desidrogenase/administração & dosagem , Malato Desidrogenase/metabolismo , Malato Desidrogenase/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/imunologia
20.
Ann Allergy Asthma Immunol ; 124(4): 333-341, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32007569

RESUMO

OBJECTIVE: To review the latest discoveries on airway epithelial cell diversity and remodeling in type 2 inflammation, including nasal polyposis. DATA SOURCES: Reviews and primary research manuscripts were identified from PubMed, Google, and Bioarchives, using the search words airway epithelium, nasal polyposis, or chronic rhinosinusitis with nasal polyposis AND basal cell, ciliated cell, secretory cell, goblet cell, neuroendocrine cell, pulmonary neuroendocrine cell, ionocyte, brush cell, solitary chemosensory cell, microvillus cell, or tuft cell. STUDY SELECTIONS: Studies were selected based on novelty and likely relevance to airway epithelial innate immune functions or the pathobiology of type 2 inflammation. RESULTS: Airway epithelial cells are more diverse than previously appreciated, with specialized subsets, including ionocytes, solitary chemosensory cells, and neuroendocrine cells that contribute to important innate immune functions. In chronic rhinosinusitis with nasal polyposis, the composition of the epithelium is significantly altered. Loss of ciliated cells and submucosal glands and an increase in basal airway epithelial progenitors leads to loss of innate immune functions and an expansion of proinflammatory potential. Type 2 cytokines play a major role in driving this process. CONCLUSION: Airway epithelial remodeling in chronic rhinosinusitis is extensive, leading to loss of innate immune function and enhanced proinflammatory potential. The mechanisms driving airway remodeling and its sequelae deserve further attention before restitution of epithelial differentiation can be considered a reasonable therapeutic target.


Assuntos
Remodelação das Vias Aéreas , Mucosa Nasal/patologia , Pólipos Nasais/patologia , Rinite/patologia , Sinusite/patologia , Doença Crônica , Humanos , Inflamação/imunologia , Inflamação/patologia , Mucosa Nasal/imunologia , Pólipos Nasais/imunologia , Rinite/imunologia , Sinusite/imunologia
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