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Lower Respiratory Tract Microbiota Diversity In Children And The Effect Of LPS On The Differentiation Of Helper T Cells In Asthmatic Mice

Posted on:2019-09-28Degree:MasterType:Thesis
Country:ChinaCandidate:L Y HouFull Text:PDF
GTID:2404330545983769Subject:Academy of Pediatrics
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Acute lower respiratory tract infections are common respiratory diseases in children,including bronchitis,pneumonia,and bronchiectasis.Among them,pneumonia is the primary cause of death among children,especially infants and young children.The prevalence of pneumonia is significantly reduced due to the use of antibiotics and vaccines.However,the overall mortality rate of pneumonia has been on the rise in recent years.The traditional laboratory testing techniques such as bacteria culture can only identify the small number of pathogenic microorganisms,and the detection of pathogens can not fully reflect the changes in the airway flora.The occurrence of pneumonia is not only related to the pathogen colonization,Dysbacteriosis also plays an important role in the process of pneumonia.The application of 16 S rDNA sequence analysis technology has brought people to a new stage in the understanding of the lower respiratory tract flora.However,little is known about the relationship between changes in pulmonary flora and pneumonia.In this study,16 S rDNA sequence analysis technique was used to detect the diversity of the distribution of lower respiratory tract microbiota in children.By detecting throat swabs and bronchoalveolar lavage fluid specimens of patients with pneumonia,it was found that the diversity of lower respiratory tract flora in pneumonia patients was significantly higher than that in the upper respiratory tract,and the abundance of lower respiratory tract flora was significantly lower than that in the upper respiratory tract.The main bacteria group that differs between bacterial pneumonia and non-bacterial pneumonia flora is the genus Haemophilus of the genus Proteobacteria,etc.KEGG metabolic pathway analysis showed that there was a significant difference in fatty acid elongation between bacterial pneumonia and non-bacterial pneumonia.Asthma is a chronic respiratory disease characterized by chronic airway inflammation,bronchial hyperresponsiveness,and reversible airway obstruction.Its specific etiology and pathogenesis have not yet been fUlly understood.Although significant progress has been made in the study of the pathogenesis and treatment of asthma,the incidence and mortality of asthma worldwide are still rising.The onset of asthma has a certain degree of familial inheritance,but the impact of complex and volatile environmental factors on asthma cannot be ignored.Environmental factors are important risk factors for asthma and asthma.The environmental triggers of asthma include air pollutants,pathogenic bacteria and their metabolites.The study found that the number of proteobacteria of Gram-negative bacteria in asthma patients was significantly higher than that in healthy humans.Among them,Haemophilus spp.was closely related to the acute attack of asthma.Lipopolysaccharide(LPS)is a common component of the cell wall of gram-negative bacteria and is also a major pathogenic component of Gram-negative bacteria.It is known that airway LPS exposure levels determine the type of immune response in asthma models.High concentration of LPS induces Thl-type immune responses,and low concentrations of LPS induces Th2-type immune responses.In the past,it was thought that Thl/Th2 imbalance was the main immunological mechanism of asthma.In recent years,the imbalance of Thl7/regulatory T(Treg)cells has also been shown to play an important role.In this study,a classic short-term asthma model was established to administer lowdose LPS during the asthma challenge.It was found that under the stimulation of LPS,the limg tissues of asthmatic mice showed obvious inflammatory cell infiltration,and the pathology of tissue edema and mucus secretion increased.Performance;real-time fluorescence quantitative experiments found that tihe expression of BATF(Th 17 transcription factor)and RORA(Thl7 transcription factor)decreased significantly at low concentrations of LPS.The expression of STAT5(Treg transcription factor)and FoxP3(Treg cytokine)in LCL group was significantly higher than that in asthma group.ELISA experiment found that the concentration of IL-17 A decreased under the effect of low concentration of LPS? and the concentration of TGF-P in LCL group was higher than that of asthma group.The experimental results showed that the differentiation of ThO cells into Treg cells was significantly increased in asthmatic mice under the influence of LPS,and the differentiation to Thl7 cells was significantly reduced.In other words,the proportion of Thl7/Treg decreased with low concentration of LPS,which may reduce the immune response to asthma.This topic is of great significance for us to further understand the mechanism of action of LPS on asthma and to clarify the clinical features of astiima under the influence of LPS,and to provide a theoretical basis and possible interventions for LPS to relieve asthma symptoms.
Keywords/Search Tags:Pneumonia, Lower respiratory tract, Bacterial flora, 16S rDNA, Asthma, LPS, Pathogenesis, Helper T cell
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