Relationship of Microbial Profile With Airway Immune Response in Eosinophilic or Neutrophilic Inflammation of Asthmat

다국어 초록 (Multilingual Abstract)

Purpose: Different characteristics of airway microbiome in asthmatics may lead to differential immune responses, which in turn cause eosinophilic or neutrophilic airway inflammation. However, the relationships among these factors have yet to be fully elucidated.
Methods: Microbes in induced sputum samples were subjected to sequence analysis of 16S rRNA. Airway inflammatory phenotypes were defined as neutrophils (>60%) and eosinophils (>3%), and inflammation endotypes were defined by levels of T helper (Th) 1 (interferon-γ), Th2 (interleukin [IL]-5 and IL-13), Th-17 (IL-17), and innate Th2 (IL-25, IL-33, and thymic stromal lymphopoietin) cytokines, inflammasomes (IL-1β), epithelial activation markers (granulocyte-macrophage colony-stimulating factor and IL-8), and Inflammation (IL-6 and tumor necrosis factor-α) cytokines in sputum supernatants was assessed by enzyme-linked immunosorbent assay.
Results: The numbers of operational taxonomic units were significantly higher in the mixed (n = 21) and neutrophilic (n = 23) inflammation groups than in the paucigranulocytic inflammation group (n = 19; p < 0.05). At the species level, Granulicatella adiacens, Streptococcus parasanguinis, Streptococcus pneumoniae, Veillonella rogosae, Haemophilus parainfluenzae, and Neisseria perflava levels were significantly higher in the eosinophilic inflammation group (n = 20), whereas JYGU_s levels were significantly higher in the neutrophilic inflammation group compared to the other subtypes (P < 0.05). Additionally, IL-5 and IL-13 concentrations were correlated with the percentage of eosinophils (P < 0.05) and IL-13 levels were positively correlated with the read counts of Porphyromonas pasteri and V. rogosae (P < 0.05). IL-1β concentrations were correlated with the percentage of neutrophils (P < 0.05). had a tendency to be positively correlated with the read count of JYGU_s (P = 0.095), and was negatively correlated with that of S. pneumoniae (P < 0.05).
Conclusions: Difference of microbial patterns in airways may induce distinctive endotypes of asthma, which is responsible for the neutrophilic or eosinophilic inflammation in asthma.

참고문헌 (Reference)

• 1 Herlemann DP, "Transitions in bacterial communities along the 2000km salinity gradient of the Baltic Sea" 5 : 1571-1579, 2011
• 2 Goleva E, "The effects of airway microbiome on corticosteroid responsiveness in asthma" 188 : 1193-1201, 2013
• 3 Manni ML, "The complex relationship between inflammation and lung function in severe asthma" 7 : 1186-1198, 2014
• 4 Delwiche EA, "The Veillonellae : Gram-negative cocci with a unique physiology" 39 : 175-193, 1985
• 5 Maliszewska-Kordybach B, "Sources, concentrations, fate and effects of polycyclic aromatic hydrocarbons (PAHs) in the environment. Part A: PAHs in air" 8 : 131-136, 1999
• 6 Choi JS, "Role of neutrophils in persistent airway obstruction due to refractory asthma" 17 : 322-329, 2012
• 7 Simpson JL, "Reduced antiviral interferon production in poorly controlled asthma is associated with neutrophilic inflammation and high-dose inhaled corticosteroids" 149 : 704-713, 2016
• 8 Karched M, "Proteomic analysis and virulence assessment of Granulicatella adiacens secretome" 9 : 104-, 2019
• 9 Green BJ, "Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma" 9 : e100645-, 2014
• 10 Tliba O, "Paucigranulocytic asthma : uncoupling of airway obstruction from inflammation" 143 : 1287-1294, 2019
• 11 Erzurum SC, "New insights in oxidant biology in asthma" 13 (13): S35-S35, 2016
• 12 Nathan C, "Neutrophils and immunity : challenges and opportunities" 6 : 173-182, 2006
• 13 Yang X, "Neutrophilic asthma is associated with increased airway bacterial burden and disordered community composition" 2018 : 9230234-, 2018
• 14 Brinkmann V, "Neutrophil extracellular traps kill bacteria" 303 : 1532-1535, 2004
• 15 Pavord ID, "Multiple inflammatory hits and the pathogenesis of severe airway disease" 27 : 884-888, 2006
• 16 Slevogt H, "Moraxella catarrhalis is internalized in respiratory epithelial cells by a trigger-like mechanism and initiates a TLR2-and partly NOD1-dependent inflammatory immune response" 9 : 694-707, 2007
• 17 Su YC, "Moraxella catarrhalis : from interactions with the host immune system to vaccine development" 7 : 1073-1100, 2012
• 18 Park H, "Microbial communities in the upper respiratory tract of patients with asthma and chronic obstructive pulmonary disease" 9 : e109710-, 2014
• 19 Hansel TT, "Microbes and mucosal immune responses in asthma" 381 : 861-873, 2013
• 20 Rogers GB, "Interpreting infective microbiota : the importance of an ecological perspective" 21 : 271-276, 2013
• 21 Hams E, "Innate type 2 cells and asthma" 12 : 503-509, 2012
• 22 Simpson JL, "Inflammatory subtypes in asthma : assessment and identification using induced sputum" 11 : 54-61, 2006
• 23 Taylor SL, "Inflammatory phenotypes in patients with severe asthma are associated with distinct airway microbiology" 141 : 94-103.e15, 2018
• 24 Besnard AG, "Inflammasome-IL-1-Th17 response in allergic lung inflammation" 4 : 3-10, 2012
• 25 Reis AC, "Induction of eosinophil apoptosis by hydrogen peroxide promotes the resolution of allergic inflammation" 6 : e1632-, 2015
• 26 Otero C, "Immune response to Streptococcus pneumoniae in asthma patients : comparison between stable situation and exacerbation" 173 : 92-101, 2013
• 27 Gauvreau GM, "Haemopoietic processes in allergic disease : eosinophil/basophil development" 39 : 1297-1306, 2009
• 28 Hirata SI, "Gut microbiome, metabolome, and allergic diseases" 66 : 523-528, 2017
• 29 Clapp WD, "Grain dust-induced airflow obstruction and inflammation of the lower respiratory tract" 150 : 611-617, 1994
• 30 Bateman ED, "Global strategy for asthma management and prevention : GINA executive summary" 31 : 143-178, 2008
• 31 ten Brinke A, "Factors associated with persistent airflow limitation in severe asthma" 164 : 744-748, 2001
• 32 Kim YS, "Extracellular vesicles, especially derived from Gram-negative bacteria, in indoor dust induce neutrophilic pulmonary inflammation associated with both Th1 and Th17 cell responses" 43 : 443-454, 2013
• 33 Schleimer RP, "Epithelium : at the interface of innate and adaptive immune responses" 120 : 1279-1284, 2007
• 34 Brightling CE, "Eosinophils, bronchitis and asthma : pathogenesis of cough and airflow obstruction" 24 : 324-327, 2011
• 35 Fahy JV, "Eosinophilic and neutrophilic inflammation in asthma : insights from clinical studies" 6 : 256-259, 2009
• 36 Veiga-Malta I, "Enolase from Streptococcus sobrinus is an immunosuppressive protein" 6 : 79-88, 2004
• 37 Reed CE, "Endotoxin-stimulated innate immunity : a contributing factor for asthma" 108 : 157-166, 2001
• 38 Simpson JL, "Elevated expression of the NLRP3 inflammasome in neutrophilic asthma" 43 : 1067-1076, 2014
• 39 Hur M, "Effect of genetically modified poplars on soil microbial communities during the phytoremediation of waste mine tailings" 77 : 7611-7619, 2011
• 40 Pérez-Losada M, "Dual transcriptomic profiling of host and microbiota during health and disease in pediatric asthma" 10 : e0131819-, 2015
• 41 Kuschner WG, "Dose-dependent cigarette smoking-related inflammatory responses in healthy adults" 9 : 1989-1994, 1996
• 42 Hilty M, "Disordered microbial communities in asthmatic airways" 5 : e8578-, 2010
• 43 Jakubovics NS, "Differential binding specificities of oral streptococcal antigen I/II family adhesins for human or bacterial ligands" 55 : 1591-1605, 2005
• 44 Kara D, "Differences between single-and dual-species biofilms of Streptococcus mutans and Veillonella parvula in growth, acidogenicity and susceptibility to chlorhexidine" 114 : 58-63, 2006
• 45 Park SW, "Development of chronic airway obstruction in patients with eosinophilic bronchitis : a prospective follow-up study" 125 : 1998-2004, 2004
• 46 Rosan B, "Dental plaque formation" 2 : 1599-1607, 2000
• 47 Jo WK, "Comparison of outdoor and indoor mobile sourcerelated volatile organic compounds between low-and high-floor apartments" 92 : 166-171, 2003
• 48 Essilfie AT, "Combined Haemophilus influenzae respiratory infection and allergic airways disease drives chronic infection and features of neutrophilic asthma" 67 : 588-599, 2012
• 49 de Vries SP, "Characterization of the molecular interplay between Moraxella catarrhalis and human respiratory tract epithelial cells" 8 : e72193-, 2013
• 50 Miki-Hosokawa T, "CD69 controls the pathogenesis of allergic airway inflammation" 183 : 8203-8215, 2009
• 51 Martín P, "CD69 : an unexpected regulator of TH17 cell-driven inflammatory responses" 4 : pe14-, 2011
• 52 Marri PR, "Asthma-associated differences in microbial composition of induced sputum" 131 : 346-352, 2013
• 53 Pang Z, "Airway microbiome in different inflammatory phenotypes of asthma : a cross-sectional study in Northeast China" 16 : 477-485, 2019
• 54 Simpson JL, "Airway dysbiosis : Haemophilus influenzae and Tropheryma in poorly controlled asthma" 47 : 792-800, 2016
• 55 Janda JM, "16S rRNA gene sequencing for bacterial identification in the diagnostic laboratory : pluses, perils, and pitfalls" 45 : 2761-2764, 2007