慢性鼻-鼻窦炎细菌生物膜与Th17/Treg失衡的研究

李晗; 孙希才; 刘全; 李艳青; 胡俐; 于华鹏; 王德辉

doi:10.13201/j.issn.1001-1781.2018.24.006

慢性鼻-鼻窦炎细菌生物膜与Th17/Treg失衡的研究

- 复旦大学附属眼耳鼻喉科医院耳鼻咽喉科(上海, 200031)
基金项目:
国家自然科学基金项目 (No:81600783)

上海市科委资助项目 (No:15401971500)

详细信息

通讯作者: 王德辉, E-mail:wangdehuient@sina.com

中图分类号: R765.4

收稿日期: 2018-08-09

Involvement of Th17/Treg imbalance in bacterial biofilm induced chronic rhinosinusitis

- Department of Otolaryngology, Affiliated Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, 200031, China

More Information

Corresponding author: WANG Dehui, E-mail: wangdehuient@sina.com

Received Date: 09 August 2018

摘要

摘要: 目的: 探讨Th17/Treg失衡在细菌生物膜(BBF)参与的慢性鼻-鼻窦炎(CRS)发病中的作用。方法: 收集CRS鼻窦黏膜,以激光共聚焦显微镜(CSLM)检测BBF,选取BBF阳性和阴性者各20例,正常鼻腔鼻窦黏膜10例,Real-time PCR法检测叉状头转录因子3(Foxp3)、维甲酸相关孤核受体γt(RORγt)、IL-17的mRNA表达,分别比较CRS组与对照组、BBF阳性组和BBF阴性组的差异。相关性分析研究基因表达之间的关系。结果: CRS组与对照组相比Foxp3 mRNA降低(P<0.05),提示Treg细胞功能减弱;两组之间的IL-17和RORγt的mRNA水平无差异(P>0.05)。BBF阳性组与BBF阴性组相比,Foxp3 mRNA降低,IL-17 mRNA升高(均P<0.05),提示Th17细胞功能增强,Treg细胞功能减弱;两组之间RORγt mRNA水平无差异(P>0.05)。Foxp3与IL-17 mRNA水平呈负相关(r=-0.283,P<0.05);Foxp3和RORγt、IL-17和RORγt的mRNA水平无显著相关性(P>0.05)。结论: BBF引起CRS鼻窦黏膜Th17/Treg失衡,可能是CRS的重要致病因素。
- 鼻窦炎 /
- 细菌生物膜 /
- 激光共聚焦显微镜 /
- Th17/Treg细胞
Abstract: Objective: The aim of this study is to investigate the involvement of Th17/Treg imbalance in the pathogenesis of bacterial biofilm (BBF) induced chronic rhinosinusitis(CRS). Method: CRS nasal sinus mucosa was collected, and BBF was examined by BacLight/CSLM detection. Forty CRS cases(20 BBF positive cases and 20 negative cases) and 10 controls were enrolled. Clinical data were recorded before operation, and nasal sinus mucosa was collected during operation. The mRNA level of Forkhead box protein 3(Foxp3), retinoid-related orphan nuclear receptor γt (RORγt), and IL-17 were detected by Real-time PCR. The differences between CRS and controls, as well as BBF positive and BBF negative group were analyzed. Correlation analysis was conducted to study the relationship between gene expression. Result: The Foxp3 mRNA was decreased in the CRS group compared with the control group (P<0.05), suggesting that the function of Treg cells was weakened. there was no difference in the mRNA level of IL-17 and RORγt between the two groups (P>0.05). Compared with the BBF-negative group, the Foxp3 mRNA was decreased and the IL-17 mRNA was increased in the BBF-positive group (P<0.05), suggesting that Th17 cells function enhanced and Treg cells function decreased. The mRNA level of RORγt showed no difference (P>0.05). The mRNA level of Foxp3 and IL-17 was negatively correlated (r=-0.283, P<0.05).Conclusion: The imbalance of Th17/Treg in sinus mucosa caused by BBF may play an important role in CRS.
- sinusitis /
- bacterial biofilm /
- laser confocal microscope /
- Th17/Treg cell

HTML全文

参考文献(30)

[1]	BHATTACHARYYA N, GILANI S.Prevalence of Potential Adult Chronic Rhinosinusitis Symptoms in the United States[J].Otolaryngol Head Neck Surg, 2018, 159:522-525.
[2]	JAMAL M, AHMAD W, ANDLEEB S, et al.Bacterial biofilm and associated infections[J].J Chin Med Assoc, 2018, 81:7-11.
[3]	KARUNASAGAR A, GARAG S S, APPANNAVARS B, et al.Bacterial Biofilms in Chronic Rhinosinusitis and Their Implications for Clinical Management[J].Indian J Otolaryngol Head Neck Surg, 2018, 70:43-48.
[4]	DLUGASZEWSKA J, LESZCZYNSKA M, LEN-KOWSKI M, et al.The pathophysiological role of bacterial biofilms in chronic sinusitis[J].Eur Arch Otorhinolaryngol, 2016, 273:1989-1994.
[5]	WU D, WANG J, ZHANG M.Altered Th17/Treg Ratio in Nasal Polyps With Distinct Cytokine Profile:Association With Patterns of Inflammation and Mucosal Remodeling[J].Medicine (Baltimore), 2016, 95:e2998.
[6]	TANTILIPIKORN P, SOOKRUNG N, MUANG-SOMBOON S, et al.Endotyping of Chronic Rhinosinusitis With and Without Polyp Using Transcription Factor Analysis[J].Front Cell Infect Microbiol, 2018, 27:82.
[7]	THOMAS M, YAWN B P, PRICE D, et al.EPOS Primary Care Guidelines:European Position Paper on the Primary Care Diagnosis and Management of Rhinosinusitis and Nasal Polyps 2007-a summary[J].Prim Care Respir J, 2008, 17:79-89.
[8]	TAJUDEEN B A, SCHWARTZ J S, PALMER J N.Understanding biofilms in chronic sinusitis[J].Curr Allergy Asthma Rep, 2016, 16:10.
[9]	CANTERO D, COOKSLEY C, BASSIOUNI A, et al.Staphylococcus aureus biofilms induce apoptosis and expression of interferon-gamma, interleukin-10, and interleukin-17A on human sinonasal explants[J].Am J Rhinol Allergy, 2015, 29:23-28.
[10]	底瑞青, 董栋, 叶琳, 等.金黄色葡萄球菌生物膜对人离体鼻窦黏膜溶菌酶、分泌性白细胞蛋白酶抑制剂和糖蛋白340表达的影响[J].临床耳鼻咽喉头颈外科杂志, 2016, 30 (3):194-199.
[11]	李宏梅, 薛金梅.金黄色葡萄球菌在难治性鼻-鼻窦炎发病机制中的作用[J].临床耳鼻咽喉头颈外科杂志, 2017, 31 (5):404-408.
[12]	FELDEN B, CATTOIR V.Bacterial Adaptation to Antibiotics through Regulatory RNAs[J].Antimicrob Agents Chemother, 2018, 62.pii:e02503-17.
[13]	ZHU X, LI S, ZHANG Q, et al.Correlation of increased Th17/Treg cell ratio with endoplasmic reticulum stress in chronic kidney disease[J].Medicine (Baltimore), 2018, 97:e10748.
[14]	KNOCHELMANN H M, DWYER C J, BAILEY S R, et al.When worlds collide:Th17 and Treg cells in cancer and autoimmunity[J].Cell Mol Immunol, 2018, 15:458-469.
[15]	HASAN M, NEUMANN B, HAUPELTSHOFER S, et al.Activation of TGF-beta-induced non-Smad signaling pathways during Th17 differentiation[J].Immunol Cell Biol, 2015, 93:662-672.
[16]	LEE G R.The Balance of Th17 versus Treg Cells in Autoimmunity[J].Int J Mol Sci, 2018, 19.pii:E730.
[17]	SILVA-GUTIERREZ N, BAHSAS ZAKY R, BOU-CHARD M, et al.T-cell profiles elicited by Toxoplasma gondii in acutely/chronically infected humans[J].Parasite Immunol, 2018, 40:e12532.
[18]	宋辉, 顾兆伟, 赵鹤, 等.卵清蛋白致敏的变应性鼻炎小鼠鼻黏膜IL-17mRNA/蛋白、RORγt、Foxp3 mR-NA表达水平的研究[J].免疫学杂志, 2016, 32 (1):60-63.
[19]	RICH H E, ALCORN J F.IL-17 Strikes a Chord in Chronic Obstructive Pulmonary Disease Exacerbation[J].Am J Respir Cell Mol Biol, 2018, 58:669-670.
[20]	KRISHNAMOORTHY N, DOUDA D N, BRUGGE-MANN T R, et al.Neutrophil cytoplasts induce TH17 differentiation and skew inflammation toward neutrophilia in severe asthma[J].Sci Immunol, 2018, 3.pii:eaao4747.
[21]	MILJKOVIC D, PSALTIS A, WORMALD P J, et al.T regulatory and Th17 cells in chronic rhinosinusitis with polyps[J].Int Forum Allergy Rhinol, 2016, 6:826-834.
[22]	SHEN Y, TANG X Y, YANG Y C, et al.Impaired balance of Th17/Treg in patients with nasal polyposis[J].Scand J Immunol, 2011, 74:176-185.
[23]	王娅, 王悦, 马永明, 等.Th9和Th17及Treg细胞在鼻息肉发病中的研究与探讨[J].临床耳鼻咽喉头颈外科杂志, 2016, 30 (4):277-281.
[24]	SEIF F, GHALEHBAGHI B, AAZAMI H, et al.Frequency of CD4 (+) and CD8 (+) T cells in Iranian chronic rhinosinusitis patients[J].Allergy Asthma Clin Immunol, 2018, 14:47.
[25]	王扬, 唐臻臻, 姚东方, 等.Th17细胞在慢性鼻-鼻窦炎中的研究进展[J].临床耳鼻咽喉头颈外科杂志, 2016, 30 (2):161-166.
[26]	WANG G Q, WANG L, ZHANG H L, et al.Stimulation of bacterial biofilms on Th17 immune cells[J].Genet Mol Res, 2015, 14:7721-7726.
[27]	BIELEN K, S JONGERS B, BODDAERT J, et al.Biofilm-Induced Type 2 Innate Immunity in a Cystic Fibrosis Model of Pseudomonas aeruginosa[J].Front Cell Infect Microbiol, 2017, 7:274.
[28]	LI X H, LEE J H.Antibiofilm agents:A new perspective for antimicrobial strategy[J].J Microbiol, 2017, 55:753-766.
[29]	HU X, HUANG Y Y, WANG Y, et al.Antimicrobial Photodynamic Therapy to Control Clinically Relevant Biofilm Infections[J].Front Microbiol, 2018, 9:1299.
[30]	ZHANG H, DAI Y, LIU Y, et al.Helicobacter pylori Colonization Protects Against Chronic Experimental Colitis by Regulating Th17/Treg Balance[J].Inflamm Bowel Dis, 2018, 24:1481-1492.