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研究生：	趙文震 Chao, Wen-Cheng
論文名稱：	探討吞噬細胞活性氧化物於分枝桿菌肉芽腫發炎中所扮演角色 The role of granulocyte-produced reactive oxygen species in mycobacterium-induced granulomatous inflammation
指導教授：	謝奇璋 Shieh, Chi-Chang
學位類別：	博士 Doctor
系所名稱：	醫學院 - 臨床醫學研究所 Institute of Clinical Medicine
論文出版年：	2016
畢業學年度：	104
語文別：	英文
論文頁數：	110
中文關鍵詞：	結核、活性氧化物、肉芽腫發炎、介白素-1β 、白血球弹性蛋白酶
外文關鍵詞：	tuberculosis, reactive oxygen species, granuloma, interleukin-1β, neutrophil elastase
相關次數：	點閱：165 下載：0
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結核病在台灣及全世界一直都是重要的傳染性疾病，糖尿病合併結核更是當前亞洲地區結核控制之重要挑戰。流行病學發現糖尿病患者感染結核容易發生開洞性肺部病灶及延緩之痰液陰轉。我們過去的研究則發現吞噬細胞產生活性氧化物能力低下是其致病機制之一。因此本研究旨在探討活性氧化物於分枝桿菌感染時所扮演之角色。
我們以一吞噬細胞無法產生活性氧化物之Ncf1-/-小鼠及一相當類似結核之分枝桿菌 (M. marinum)建立一小鼠感染模式。相對於正常小鼠，Ncf1-/-小鼠無法控制分枝桿菌生長，有明顯之體重下降及高死亡率。缺乏活性氧化物狀態下早期發炎即有大量白血球浸潤並導致肉芽腫發炎之結構較為鬆散。我們發現Ncf1-/-小鼠除肺部有大量白血球驅化激素外也相當大量之介白素-1β產生。這個發現和我們過去細胞實驗時以巨噬細胞感染分枝桿菌時發現活性氧化物缺乏會導致發炎小體活化下降及介白素-1β產生下降有所不同，暗示著活體內中應有巨噬細胞發炎小體活化以外之之機制調控介白素-1β產生。我們接著發現相對於正常小鼠，Ncf1-/-小鼠肺部較多之白血球弹性蛋白酶，這是一個源自白血球已被證實可活化介白素-1β之前驅物成為為活性介白素-1β之蛋白酶。另外我們也在人類結核感染的肺部乾酪性壞死組織及週遭發炎組織發現大量白血球弹性蛋白酶陽性細胞。此外我們以單株抗體去除介白素-1β之小鼠實驗發現去除介白素-1β可顯著降低肺部組織發炎，因此目前可調控介白素-1β之生物製劑未來應有可能應用於減緩肺結核患者發炎之使用。
本研究發現白血球於分枝桿菌感染導致組織發炎之關鍵角色及其調控介白素-1β之機制，此結果將有助於未來研發藥物以調控分枝桿菌對肺部所造成之損傷。

Mycobacterium tuberculosis (TB) is still a leading infectious disease in Taiwan and the world, and the convergence of TB and diabetes mellitus (DM) is a growing global challenge, particularly in Asia. Patients with DMTB are characterized by the formation of large pulmonary cavities and slow sputum conversion, and our previous studies have shown an impaired reactive oxygen species (ROS) production by granulocytes in patients with DMTB. We hence aimed to investigate the role of ROS in mycobacterial infection.
We established a mouse model to study the role of ROS in mycobacterial infection by using ROS-deficient mice (Ncf1-/-) and M. marinum, a close relative to M. tuberculosis. We found that Ncf1-/- mice had poor mycobacterial control, more severe weight loss, and higher mortality than those in WT mice. The impaired ROS generation led to the early influx of neutrophils resulting in a less compact granulomatous inflammation. In addition to high levels of neutrophilic chemokines, the elevation of IL-1β was found in the lungs of Ncf1-/- mice. Our previous in vitro study found that ROS regulates M. marinum-induced inflammasome activation leading to a low IL-1β production of macrophages; therefore, inflammasome-independent pathway might exist in M. marinum-infected Ncf1-/-mice. We found the abundance of neutrophil elastase (NE), a proved neutrophil-derived protease to cleave pro-IL-1β into active IL-1β, in the lungs of M. marinum-infected Ncf1-/-mice. Moreover, we demonstrated similar abundant NE-positive cells in human pulmonary TB infection. Additionally, we showed that depletion of IL-1β reduces pulmonary inflammation in both WT and Ncf1-/-mice; therefore, IL-1β may be a potential target of host-directed therapy in TB to alleviate mycobacterium-related destructive inflammation.
This study sheds lights on long-sought mechanisms of how neutrophil to exert destructive inflammation in mycobacterial infection and provides an inflammasome-independent pathway of IL-1β production, which will be critical in the future to design precision medication as an adjunctive host-directed therapy targeting on IL-1β signaling.

Chapter 1. Introduction ………………………………………1
1.1. Epidemiology and challenges of tuberculosis infection ………………………...1
  1.1.1 Epidemiology of tuberculosis in Taiwan and the world ……………………….1
  1.1.2 Convergence of diabetes mellitus and tuberculosis in Asian countries ……......2
  1.1.3. Unique clinical manifestations of TB infection in subjects with DM………….3
1.2. Immunological basis of TB infection……………………………………………..4
  1.2.1 Revisiting granulomatous inflammation ……………………………………….4 
  1.2.2 The role of neutrophils in TB infection ………………………………………...6
  1.2.3 Inflammatory networks and dysregulated inflammation in TB infection ………7
  1.2.4 Animal models to investigate TB pathogenesis ………...………………………9
1.3. Immune mechanisms underlying DMTB ……………………………………….10
  1.3.1 Current evidence for DMTB pathogenesis in animal models ………………....10
  1.3.2 The role of ROS in subjects with DMTB ………………………..………….…11
1.4. The roles of ROS-IL-1β in TB immunity ……………………………………….12
  1.4.1 The pivotal role of IL-1β in mycobacterial infection ………………………….12  
  1.4.2 ROS- IL1β axis in mycobacterial infection ……………………………………13 
  1.4.3 Inflammasome-independent IL-1β production in mycobacterial infection…….14
1.5. The goal of this study…………………………………………………………......16

Chapter 2. Outcome correlation of smear-positivity but culture-negativity during standard anti-tuberculosis chemotherapy in Taiwan ……………………………………...17
2.1 Backgrounds and Aims …………………………………………………………..17
2.2 Materials and Methods …………………………………………………………...20
2.3 Results …………………………………………………………………………..…23
2.4 Discussion …………………………………………………………………………27
2.5 Figures and Tables ………………………………………………………………..33

Chapter 3. ROS-deficiency leads to the early neutrophilic pulmonary inflammation in mycobacterial infection ……….42
3.1 Backgrounds and Aims …………………………………………………………..42
3.2 Materials and Methods …………………………………………………………..45
3.3 Results ……………………………………………………………………………..50
3.4 Discussion ………………………………………………………………………….55
3.5 Figures ……………………………………………………………………………..61

Chapter 4. Neutrophil interacts with macrophage through IL-1β production in ROS-deficient status ………………….69
4.1 Backgrounds and Aims …………………………………………………………69
4.2 Materials and Methods …………………………………………………………72
4.3 Results ……………………………………………………………………………74
4.4 Discussion ………………………………………………………………………..78
4.5 Figures ……………………………………………………………………………84

Chapter 5. General Discussion, Conclusion, and Prospects ..91
5.1 Experimental findings ………………………………………………………….…91 
5.1.1 Sputum SPCN reflects unique host-pathogen interactions in DMTB……..…91 
5.1.2 ROS-deficiency plays a pivotal role in the formation of granuloma ………..92
5.1.3 Neutrophil exerts detrimental inflammation through regulation of IL-1β…..92
5.2 Methodological considerations ……………………………………………….…93 
5.2.1 Animal model in mycobacterial infection ………………………………….93
5.2.2 M. marinum as a surrogate of M. tb in studying IL-1β pathway …………..95 
5.3 Prospects ………………………………………………………………………….95
5.4 Figure ……………………………………………………………………………..97
Bibliography ……………………………………………….......99
Publication lists ………………………………………………110 
List of Figures 
Figure 2.1 Flow chart of the subjects enrollment process ………………………….…33
Figure 2.2 DM correlates with cavity formation in subjects with TB …………………34
Figure 2.3 The cross-over of smear- and culture-conversion in TB subjects with DM or cavity formation……………………………………………………………35
Figure 2.4 Formation of the cavity and high AFS grade correlates with sputum SPCN..36
Figure 3.1 M. marinum infection leads to severe weight loss and high mortality in Ncf1-/- mice ………………………………………………………………………..61
Figure 3.2 A higher level of pulmonary inflammation in Ncf1-/- mice compared those in WT mice ………………………………………………………………..…63
Figure 3.3 More extensive inflammation and positive acid-fast stain bacilli in Ncf1-/- mice than those in WT mice ……………………………………………….64
Figure 3.4 The loose and neutrophilc granuloma in Ncf1-/- mice compared with the compact granuloma in WT mice …………………………………………..65
Figure 3.5 Quantification of early neutrophilic influx in Ncf1-/- mice …………………66
Figure 3.6 High IL-1β and neutrophilc chemokines in the early phase of M. marinum-infected Ncf1-/- mice ……………………………………………..68
Figure 4.1 Lack of ROS reduces and IL-1β production in ROS-deficient mouse macrophages ……..………………………………………………………...84
Figure 4.2 ROS-regulated inflammasome activation and IL-1β production in THP-1 cells derived macrophages …………………….……………………..……85
Figure 4.3 More neutrophil elastase was found in the lungs of M. marinum-infected Ncf1-/- mice than those in WT mice …………………………..……………86
Figure 4.4 Depletion of IL-1β alleviates the tissue inflammation in both M. marinum-infected Ncf1-/- and WT mice ……………………………...…….88
Figure 4.5 Neutrophils within the caseous granulomatous inflammation of human pulmonary tuberculosis infection ………………………………………….89
Figure 4.6 Neutrophil elastase is abundant in the caseous granulomatous inflammation of human pulmonary tuberculosis infection …………………………….…90
Figure 5.1 Schematic diagram of the proposed mechanism ……………………………97
 
List of Tables 
Table 2.1 Characteristics of subjects with and without sputum SPCN during treatment.........................................................................................................37
Table 2.2 Multivariate logistic regression of clinical predisposing factors for sputum SPCN in TB subjects……………………………………………………...…38
Table 2.3 Multivariate logistic regression of all factors for sputum SPCN in TB subjects……………………………………………………………………….39
Table 2.4 Anti-TB chemotherapy and outcome of subjects with and without sputum SPCN ………………………………………………………………………..40
Table 2.5 Characteristics of the 10 subjects who relapses ……………………………..41 

                                    

Adams, D. O. (1976). The granulomatous inflammatory response. A review. Am J Pathol, 84(1), 164-192.
Adams, K. N., Takaki, K., Connolly, L. E., Wiedenhoft, H., Winglee, K., Humbert, O., et al. (2011). Drug tolerance in replicating mycobacteria mediated by a macrophage-induced efflux mechanism. Cell, 145(1), 39-53. doi:10.1016/j.cell.2011.02.022
Al-Moamary, M. S., Black, W., Bessuille, E., Elwood, R. K., & Vedal, S. (1999). The significance of the persistent presence of acid-fast bacilli in sputum smears in pulmonary tuberculosis. Chest, 116(3), 726-731.
Altaf, M., Miller, C. H., Bellows, D. S., & O'Toole, R. (2010). Evaluation of the Mycobacterium smegmatis and BCG models for the discovery of Mycobacterium tuberculosis inhibitors. Tuberculosis (Edinb), 90(6), 333-337. doi:10.1016/j.tube.2010.09.002
Andrade, B. B., Pavan Kumar, N., Sridhar, R., Banurekha, V. V., Jawahar, M. S., Nutman, T. B., et al. (2014). Heightened plasma levels of heme oxygenase-1 and tissue inhibitor of metalloproteinase-4 as well as elevated peripheral neutrophil counts are associated with TB-diabetes comorbidity. Chest, 145(6), 1244-1254. doi:10.1378/chest.13-1799
Annual Report, Taiwan Centers for Disease Control. (2016). Retrieved from http://www.cdc.gov.tw/uploads/files/201509/0cc797c3-5252-477f-bd33-91b68c62238d.pdf.
Baek, S. H., Li, A. H., & Sassetti, C. M. (2011). Metabolic regulation of mycobacterial growth and antibiotic sensitivity. PLoS Biol, 9(5), e1001065. doi:10.1371/journal.pbio.1001065
Balaban, N. Q., Merrin, J., Chait, R., Kowalik, L., & Leibler, S. (2004). Bacterial persistence as a phenotypic switch. Science, 305(5690), 1622-1625. doi:10.1126/science.1099390
Behar, S. M., & Sassetti, C. M. (2014). Immunology: Fixing the odds against tuberculosis. Nature, 511(7507), 39-40. doi:10.1038/nature13512
Biketov, S., Mukamolova, G. V., Potapov, V., Gilenkov, E., Vostroknutova, G., Kell, D. B., et al. (2000). Culturability of Mycobacterium tuberculosis cells isolated from murine macrophages: a bacterial growth factor promotes recovery. FEMS Immunol Med Microbiol, 29(4), 233-240.
Cadena, A. M., Flynn, J. L., & Fortune, S. M. (2016). The Importance of First Impressions: Early Events in Mycobacterium tuberculosis Infection Influence Outcome. MBio, 7(2). doi:10.1128/mBio.00342-16
Canetti, G. (1955). The Tubercle Bacillus in the Pulmonary Lesion of Man: Histobacteriology and its Bearing on the Therapy of Pulmonary Tuberculosis. Retrieved from New York:
Carlsson, F., Kim, J., Dumitru, C., Barck, K. H., Carano, R. A., Sun, M., et al. (2010). Host-detrimental role of Esx-1-mediated inflammasome activation in mycobacterial infection. PLoS Pathog, 6(5), e1000895. doi:10.1371/journal.ppat.1000895
Cassel, S. L., Joly, S., & Sutterwala, F. S. (2009). The NLRP3 inflammasome: a sensor of immune danger signals. Semin Immunol, 21(4), 194-198. doi:10.1016/j.smim.2009.05.002
Chang, J. T., Dou, H. Y., Yen, C. L., Wu, Y. H., Huang, R. M., Lin, H. J., et al. (2011). Effect of type 2 diabetes mellitus on the clinical severity and treatment outcome in patients with pulmonary tuberculosis: a potential role in the emergence of multidrug-resistance. J Formos Med Assoc, 110(6), 372-381. doi:10.1016/S0929-6646(11)60055-7
Chao, W. C., Yen, C. L., Wu, Y. H., Chen, S. Y., Hsieh, C. Y., Chang, T. C., et al. (2015). Increased resistin may suppress reactive oxygen species production and inflammasome activation in type 2 diabetic patients with pulmonary tuberculosis infection. Microbes Infect, 17(3), 195-204. doi:10.1016/j.micinf.2014.11.009
Chen, C. C., Tsai, S. H., Lu, C. C., Hu, S. T., Wu, T. S., Huang, T. T., et al. (2012). Activation of an NLRP3 inflammasome restricts Mycobacterium kansasii infection. PLoS One, 7(4), e36292. doi:10.1371/journal.pone.0036292
Chiang, C. Y., Bai, K. J., Lin, H. H., Chien, S. T., Lee, J. J., Enarson, D. A., et al. (2015). The influence of diabetes, glycemic control, and diabetes-related comorbidities on pulmonary tuberculosis. PLoS One, 10(3), e0121698. doi:10.1371/journal.pone.0121698
Chien, J. Y., Chen, Y. T., Shu, C. C., Lee, J. J., Wang, J. Y., Yu, C. J., et al. (2013). Outcome correlation of smear-positivity for acid-fast bacilli at the fifth month of treatment in non-multidrug-resistant TB. Chest, 143(6), 1725-1732. doi:10.1378/chest.12-2051
Chtanova, T., Schaeffer, M., Han, S. J., van Dooren, G. G., Nollmann, M., Herzmark, P., et al. (2008). Dynamics of neutrophil migration in lymph nodes during infection. Immunity, 29(3), 487-496. doi:10.1016/j.immuni.2008.07.012
Clark, S., Hall, Y., & Williams, A. (2015). Animal models of tuberculosis: Guinea pigs. Cold Spring Harb Perspect Med, 5(5), a018572. doi:10.1101/cshperspect.a018572
Collison, K. S., Parhar, R. S., Saleh, S. S., Meyer, B. F., Kwaasi, A. A., Hammami, M. M., et al. (2002). RAGE-mediated neutrophil dysfunction is evoked by advanced glycation end products (AGEs). J Leukoc Biol, 71(3), 433-444.
Corleis, B., Korbel, D., Wilson, R., Bylund, J., Chee, R., & Schaible, U. E. (2012). Escape of Mycobacterium tuberculosis from oxidative killing by neutrophils. Cell Microbiol, 14(7), 1109-1121. doi:10.1111/j.1462-5822.2012.01783.x
Dannenberg, A. M., Jr. (1994). Roles of cytotoxic delayed-type hypersensitivity and macrophage-activating cell-mediated immunity in the pathogenesis of tuberculosis. Immunobiology, 191(4-5), 461-473. doi:10.1016/S0171-2985(11)80452-3
Davis, J. M., Clay, H., Lewis, J. L., Ghori, N., Herbomel, P., & Ramakrishnan, L. (2002). Real-time visualization of mycobacterium-macrophage interactions leading to initiation of granuloma formation in zebrafish embryos. Immunity, 17(6), 693-702.
Davis, J. M., & Ramakrishnan, L. (2009). The role of the granuloma in expansion and dissemination of early tuberculous infection. Cell, 136(1), 37-49. doi:10.1016/j.cell.2008.11.014
Deffert, C., Schappi, M. G., Pache, J. C., Cachat, J., Vesin, D., Bisig, R., et al. (2014). Bacillus calmette-guerin infection in NADPH oxidase deficiency: defective mycobacterial sequestration and granuloma formation. PLoS Pathog, 10(9), e1004325. doi:10.1371/journal.ppat.1004325
Dharmadhikari, A. S., & Nardell, E. A. (2008). What animal models teach humans about tuberculosis. Am J Respir Cell Mol Biol, 39(5), 503-508. doi:10.1165/rcmb.2008-0154TR
Diagnostic Standards and Classification of Tuberculosis in Adults and Children. (2000). Am J Respir Crit Care Med, 161(4 Pt 1), 1376-1395. doi:10.1164/ajrccm.161.4.16141
Dinarello, C. A. (1996). Biologic basis for interleukin-1 in disease. Blood, 87(6), 2095-2147.
Dinarello, C. A., Simon, A., & van der Meer, J. W. (2012). Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov, 11(8), 633-652. doi:10.1038/nrd3800
Divangahi, M., Desjardins, D., Nunes-Alves, C., Remold, H. G., & Behar, S. M. (2010). Eicosanoid pathways regulate adaptive immunity to Mycobacterium tuberculosis. Nat Immunol, 11(8), 751-758. doi:10.1038/ni.1904
Dooley, K. E., & Chaisson, R. E. (2009). Tuberculosis and diabetes mellitus: convergence of two epidemics. Lancet Infect Dis, 9(12), 737-746. doi:10.1016/S1473-3099(09)70282-8
Dorhoi, A., Iannaccone, M., Farinacci, M., Fae, K. C., Schreiber, J., Moura-Alves, P., et al. (2013). MicroRNA-223 controls susceptibility to tuberculosis by regulating lung neutrophil recruitment. J Clin Invest, 123(11), 4836-4848. doi:10.1172/JCI67604
Dorhoi, A., Iannaccone, M., Maertzdorf, J., Nouailles, G., Weiner, J., 3rd, & Kaufmann, S. H. (2014). Reverse translation in tuberculosis: neutrophils provide clues for understanding development of active disease. Front Immunol, 5, 36. doi:10.3389/fimmu.2014.00036
Elkington, P. T., D'Armiento, J. M., & Friedland, J. S. (2011). Tuberculosis immunopathology: the neglected role of extracellular matrix destruction. Sci Transl Med, 3(71), 71ps76. doi:10.1126/scitranslmed.3001847
Eum, S. Y., Kong, J. H., Hong, M. S., Lee, Y. J., Kim, J. H., Hwang, S. H., et al. (2010). Neutrophils are the predominant infected phagocytic cells in the airways of patients with active pulmonary TB. Chest, 137(1), 122-128. doi:10.1378/chest.09-0903
Feldman, C., & Anderson, R. (2013). Cigarette smoking and mechanisms of susceptibility to infections of the respiratory tract and other organ systems. J Infect, 67(3), 169-184. doi:10.1016/j.jinf.2013.05.004
Flynn, J. L., Gideon, H. P., Mattila, J. T., & Lin, P. L. (2015). Immunology studies in non-human primate models of tuberculosis. Immunol Rev, 264(1), 60-73. doi:10.1111/imr.12258
Friedland, J. S. (2014). Targeting the inflammatory response in tuberculosis. N Engl J Med, 371(14), 1354-1356. doi:10.1056/NEJMcibr1408663
Gao, L. Y., & Manoranjan, J. (2005). Laboratory maintenance of Mycobacterium marinum. Curr Protoc Microbiol, Chapter 10, Unit 10B 11. doi:10.1002/9780471729259.mc10b01s00
Global tuberculosis report, World Health Organization. (2015).
Grant, S. S., & Hung, D. T. (2013). Persistent bacterial infections, antibiotic tolerance, and the oxidative stress response. Virulence, 4(4), 273-283. doi:10.4161/viru.23987
Gregory, A. D., Kliment, C. R., Metz, H. E., Kim, K. H., Kargl, J., Agostini, B. A., et al. (2015). Neutrophil elastase promotes myofibroblast differentiation in lung fibrosis. J Leukoc Biol, 98(2), 143-152. doi:10.1189/jlb.3HI1014-493R
Gross, O., Thomas, C. J., Guarda, G., & Tschopp, J. (2011). The inflammasome: an integrated view. Immunol Rev, 243(1), 136-151. doi:10.1111/j.1600-065X.2011.01046.x
Gupta, U. D., & Katoch, V. M. (2005). Animal models of tuberculosis. Tuberculosis (Edinb), 85(5-6), 277-293. doi:10.1016/j.tube.2005.08.008
Hingley-Wilson, S. M., Sambandamurthy, V. K., & Jacobs, W. R., Jr. (2003). Survival perspectives from the world's most successful pathogen, Mycobacterium tuberculosis. Nat Immunol, 4(10), 949-955. doi:10.1038/ni981
Hodgson, K., Morris, J., Bridson, T., Govan, B., Rush, C., & Ketheesan, N. (2015). Immunological mechanisms contributing to the double burden of diabetes and intracellular bacterial infections. Immunology, 144(2), 171-185. doi:10.1111/imm.12394
Horne, D. J., Johnson, C. O., Oren, E., Spitters, C., & Narita, M. (2010). How soon should patients with smear-positive tuberculosis be released from inpatient isolation? Infect Control Hosp Epidemiol, 31(1), 78-84. doi:10.1086/649022
Huang, Y. F., Liu, S. Y., Yen, C. L., Yang, P. W., & Shieh, C. C. (2009). Thapsigargin and flavin adenine dinucleotide ex vivo treatment rescues trafficking-defective gp91phox in chronic granulomatous disease leukocytes. Free Radic Biol Med, 47(7), 932-940. doi:10.1016/j.freeradbiomed.2009.06.037
Huang, Y. F., Lo, P. C., Yen, C. L., Nigrovic, P. A., Chao, W. C., Wang, W. Z., et al. (2015). Redox Regulation of Pro-IL-1beta Processing May Contribute to the Increased Severity of Serum-Induced Arthritis in NOX2-Deficient Mice. Antioxid Redox Signal, 23(12), 973-984. doi:10.1089/ars.2014.6136
Jayaraman, P., Sada-Ovalle, I., Nishimura, T., Anderson, A. C., Kuchroo, V. K., Remold, H. G., et al. (2013). IL-1beta promotes antimicrobial immunity in macrophages by regulating TNFR signaling and caspase-3 activation. J Immunol, 190(8), 4196-4204. doi:10.4049/jimmunol.1202688
Jeon, C. Y., & Murray, M. B. (2008). Diabetes mellitus increases the risk of active tuberculosis: a systematic review of 13 observational studies. PLoS Med, 5(7), e152. doi:10.1371/journal.pmed.0050152
Joosten, L. A., Netea, M. G., Fantuzzi, G., Koenders, M. I., Helsen, M. M., Sparrer, H., et al. (2009). Inflammatory arthritis in caspase 1 gene-deficient mice: contribution of proteinase 3 to caspase 1-independent production of bioactive interleukin-1beta. Arthritis Rheum, 60(12), 3651-3662. doi:10.1002/art.25006
Jou, R., Chiang, C. Y., Yu, C. Y., & Wu, M. H. (2009). Proficiency of drug susceptibility testing for Mycobacterium tuberculosis in Taiwan. Int J Tuberc Lung Dis, 13(9), 1142-1147.
Juffermans, N. P., Florquin, S., Camoglio, L., Verbon, A., Kolk, A. H., Speelman, P., et al. (2000). Interleukin-1 signaling is essential for host defense during murine pulmonary tuberculosis. J Infect Dis, 182(3), 902-908. doi:10.1086/315771
Karmakar, M., Sun, Y., Hise, A. G., Rietsch, A., & Pearlman, E. (2012). Cutting edge: IL-1beta processing during Pseudomonas aeruginosa infection is mediated by neutrophil serine proteases and is independent of NLRC4 and caspase-1. J Immunol, 189(9), 4231-4235. doi:10.4049/jimmunol.1201447
Kaufmann, S. H., & Dorhoi, A. (2013). Inflammation in tuberculosis: interactions, imbalances and interventions. Curr Opin Immunol, 25(4), 441-449. doi:10.1016/j.coi.2013.05.005
Kiran, D., Podell, B. K., Chambers, M., & Basaraba, R. J. (2016). Host-directed therapy targeting the Mycobacterium tuberculosis granuloma: a review. Semin Immunopathol, 38(2), 167-183. doi:10.1007/s00281-015-0537-x
Kisich, K. O., Higgins, M., Diamond, G., & Heifets, L. (2002). Tumor necrosis factor alpha stimulates killing of Mycobacterium tuberculosis by human neutrophils. Infect Immun, 70(8), 4591-4599.
Kurenuma, T., Kawamura, I., Hara, H., Uchiyama, R., Daim, S., Dewamitta, S. R., et al. (2009). The RD1 locus in the Mycobacterium tuberculosis genome contributes to activation of caspase-1 via induction of potassium ion efflux in infected macrophages. Infect Immun, 77(9), 3992-4001. doi:10.1128/IAI.00015-09
Lander, H. M., Milbank, A. J., Tauras, J. M., Hajjar, D. P., Hempstead, B. L., Schwartz, G. D., et al. (1996). Redox regulation of cell signalling. Nature, 381(6581), 380-381. doi:10.1038/381380a0
Leegaard, A., Riis, A., Kornum, J. B., Prahl, J. B., Thomsen, V. O., Sorensen, H. T., et al. (2011). Diabetes, glycemic control, and risk of tuberculosis: a population-based case-control study. Diabetes Care, 34(12), 2530-2535. doi:10.2337/dc11-0902
Levin, B. R., & Rozen, D. E. (2006). Non-inherited antibiotic resistance. Nat Rev Microbiol, 4(7), 556-562. doi:10.1038/nrmicro1445
Lewis, K. (2010). Persister cells. Annu Rev Microbiol, 64, 357-372. doi:10.1146/annurev.micro.112408.134306
Lin, H. H., Ezzati, M., Chang, H. Y., & Murray, M. (2009). Association between tobacco smoking and active tuberculosis in Taiwan: prospective cohort study. Am J Respir Crit Care Med, 180(5), 475-480. doi:10.1164/rccm.200904-0549OC
Lin, P. L., Pawar, S., Myers, A., Pegu, A., Fuhrman, C., Reinhart, T. A., et al. (2006). Early events in Mycobacterium tuberculosis infection in cynomolgus macaques. Infect Immun, 74(7), 3790-3803. doi:10.1128/IAI.00064-06
Maciel, E. L., Brioschi, A. P., Peres, R. L., Guidoni, L. M., Ribeiro, F. K., Hadad, D. J., et al. (2013). Smoking and 2-month culture conversion during anti-tuberculosis treatment. Int J Tuberc Lung Dis, 17(2), 225-228. doi:10.5588/ijtld.12.0426
Martens, G. W., Arikan, M. C., Lee, J., Ren, F., Greiner, D., & Kornfeld, H. (2007). Tuberculosis susceptibility of diabetic mice. Am J Respir Cell Mol Biol, 37(5), 518-524. doi:10.1165/rcmb.2006-0478OC
Martineau, A. R., Newton, S. M., Wilkinson, K. A., Kampmann, B., Hall, B. M., Nawroly, N., et al. (2007). Neutrophil-mediated innate immune resistance to mycobacteria. J Clin Invest, 117(7), 1988-1994. doi:10.1172/JCI31097
Martinez, N., & Kornfeld, H. (2014). Diabetes and immunity to tuberculosis. Eur J Immunol, 44(3), 617-626. doi:10.1002/eji.201344301
Martinon, F. (2010). Signaling by ROS drives inflammasome activation. Eur J Immunol, 40(3), 616-619. doi:10.1002/eji.200940168
Marzo, E., Vilaplana, C., Tapia, G., Diaz, J., Garcia, V., & Cardona, P. J. (2014). Damaging role of neutrophilic infiltration in a mouse model of progressive tuberculosis. Tuberculosis (Edinb), 94(1), 55-64. doi:10.1016/j.tube.2013.09.004
Mayer-Barber, K. D., Andrade, B. B., Barber, D. L., Hieny, S., Feng, C. G., Caspar, P., et al. (2011). Innate and adaptive interferons suppress IL-1alpha and IL-1beta production by distinct pulmonary myeloid subsets during Mycobacterium tuberculosis infection. Immunity, 35(6), 1023-1034. doi:10.1016/j.immuni.2011.12.002
Mayer-Barber, K. D., Andrade, B. B., Oland, S. D., Amaral, E. P., Barber, D. L., Gonzales, J., et al. (2014). Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk. Nature, 511(7507), 99-103. doi:10.1038/nature13489
Mayer-Barber, K. D., Barber, D. L., Shenderov, K., White, S. D., Wilson, M. S., Cheever, A., et al. (2010). Caspase-1 independent IL-1beta production is critical for host resistance to mycobacterium tuberculosis and does not require TLR signaling in vivo. J Immunol, 184(7), 3326-3330. doi:10.4049/jimmunol.0904189
Miao, E. A., Leaf, I. A., Treuting, P. M., Mao, D. P., Dors, M., Sarkar, A., et al. (2010). Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria. Nat Immunol, 11(12), 1136-1142. doi:10.1038/ni.1960
Mishra, B. B., Moura-Alves, P., Sonawane, A., Hacohen, N., Griffiths, G., Moita, L. F., et al. (2010). Mycobacterium tuberculosis protein ESAT-6 is a potent activator of the NLRP3/ASC inflammasome. Cell Microbiol, 12(8), 1046-1063. doi:10.1111/j.1462-5822.2010.01450.x
Morrison, J., Pai, M., & Hopewell, P. C. (2008). Tuberculosis and latent tuberculosis infection in close contacts of people with pulmonary tuberculosis in low-income and middle-income countries: a systematic review and meta-analysis. Lancet Infect Dis, 8(6), 359-368. doi:10.1016/S1473-3099(08)70071-9
Mozaffarian, D., Kamineni, A., Carnethon, M., Djousse, L., Mukamal, K. J., & Siscovick, D. (2009). Lifestyle risk factors and new-onset diabetes mellitus in older adults: the cardiovascular health study. Arch Intern Med, 169(8), 798-807. doi:10.1001/archinternmed.2009.21
Mukamolova, G. V., Turapov, O., Malkin, J., Woltmann, G., & Barer, M. R. (2010). Resuscitation-promoting factors reveal an occult population of tubercle Bacilli in Sputum. Am J Respir Crit Care Med, 181(2), 174-180. doi:10.1164/rccm.200905-0661OC
Nandi, B., & Behar, S. M. (2011). Regulation of neutrophils by interferon-gamma limits lung inflammation during tuberculosis infection. J Exp Med, 208(11), 2251-2262. doi:10.1084/jem.20110919
Nathan, C., & Ding, A. (2010). Nonresolving inflammation. Cell, 140(6), 871-882. doi:10.1016/j.cell.2010.02.029
Netea, M. G., van de Veerdonk, F. L., van der Meer, J. W., Dinarello, C. A., & Joosten, L. A. (2015). Inflammasome-independent regulation of IL-1-family cytokines. Annu Rev Immunol, 33, 49-77. doi:10.1146/annurev-immunol-032414-112306
Nguyen, C. (2004). Images in clinical medicine. Mycobacterium marinum. N Engl J Med, 350(9), e8. doi:10.1056/ENEJMicm000083
Nouailles, G., Dorhoi, A., Koch, M., Zerrahn, J., Weiner, J., 3rd, Fae, K. C., et al. (2014). CXCL5-secreting pulmonary epithelial cells drive destructive neutrophilic inflammation in tuberculosis. J Clin Invest, 124(3), 1268-1282. doi:10.1172/JCI72030
Novikov, A., Cardone, M., Thompson, R., Shenderov, K., Kirschman, K. D., Mayer-Barber, K. D., et al. (2011). Mycobacterium tuberculosis triggers host type I IFN signaling to regulate IL-1beta production in human macrophages. J Immunol, 187(5), 2540-2547. doi:10.4049/jimmunol.1100926
Oehlers, S. H., Cronan, M. R., Scott, N. R., Thomas, M. I., Okuda, K. S., Walton, E. M., et al. (2015). Interception of host angiogenic signalling limits mycobacterial growth. Nature, 517(7536), 612-615. doi:10.1038/nature13967
Olsen, N. J., & Stein, C. M. (2004). New drugs for rheumatoid arthritis. N Engl J Med, 350(21), 2167-2179. doi:10.1056/NEJMra032906
Ong, C. W., Elkington, P. T., Brilha, S., Ugarte-Gil, C., Tome-Esteban, M. T., Tezera, L. B., et al. (2015). Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human Pulmonary Tuberculosis. PLoS Pathog, 11(5), e1004917. doi:10.1371/journal.ppat.1004917
Ong, C. W., Elkington, P. T., & Friedland, J. S. (2014). Tuberculosis, pulmonary cavitation, and matrix metalloproteinases. Am J Respir Crit Care Med, 190(1), 9-18. doi:10.1164/rccm.201311-2106PP
Pan, S. C., Ku, C. C., Kao, D., Ezzati, M., Fang, C. T., & Lin, H. H. (2015). Effect of diabetes on tuberculosis control in 13 countries with high tuberculosis: a modelling study. Lancet Diabetes Endocrinol, 3(5), 323-330. doi:10.1016/S2213-8587(15)00042-X
Pasquaroli, S., Zandri, G., Vignaroli, C., Vuotto, C., Donelli, G., & Biavasco, F. (2013). Antibiotic pressure can induce the viable but non-culturable state in Staphylococcus aureus growing in biofilms. J Antimicrob Chemother, 68(8), 1812-1817. doi:10.1093/jac/dkt086
Pefura-Yone, E. W., Kengne, A. P., & Kuaban, C. (2014). Non-conversion of sputum culture among patients with smear positive pulmonary tuberculosis in Cameroon: a prospective cohort study. BMC Infect Dis, 14, 138. doi:10.1186/1471-2334-14-138
Peng, X., Knouse, J. A., & Hernon, K. M. (2015). Rabbit Models for Studying Human Infectious Diseases. Comp Med, 65(6), 499-507.
Podell, B. K., Ackart, D. F., Kirk, N. M., Eck, S. P., Bell, C., & Basaraba, R. J. (2012). Non-diabetic hyperglycemia exacerbates disease severity in Mycobacterium tuberculosis infected guinea pigs. PLoS One, 7(10), e46824. doi:10.1371/journal.pone.0046824
Podell, B. K., Ackart, D. F., Obregon-Henao, A., Eck, S. P., Henao-Tamayo, M., Richardson, M., et al. (2014). Increased severity of tuberculosis in Guinea pigs with type 2 diabetes: a model of diabetes-tuberculosis comorbidity. Am J Pathol, 184(4), 1104-1118. doi:10.1016/j.ajpath.2013.12.015
Poljsak, B., Suput, D., & Milisav, I. (2013). Achieving the balance between ROS and antioxidants: when to use the synthetic antioxidants. Oxid Med Cell Longev, 2013, 956792. doi:10.1155/2013/956792
Popkin, B. M. (2008). Will China's nutrition transition overwhelm its health care system and slow economic growth? Health Aff (Millwood), 27(4), 1064-1076. doi:10.1377/hlthaff.27.4.1064
Porcelli, S. A. (2008). Tuberculosis: Shrewd survival strategy. Nature, 454(7205), 702-703. doi:10.1038/454702a
Ramakrishnan, L. (2012). Revisiting the role of the granuloma in tuberculosis. Nat Rev Immunol, 12(5), 352-366. doi:10.1038/nri3211
Rhee, C. K., Yoo, K. H., Lee, J. H., Park, M. J., Kim, W. J., Park, Y. B., et al. (2013). Clinical characteristics of patients with tuberculosis-destroyed lung. Int J Tuberc Lung Dis, 17(1), 67-75. doi:10.5588/ijtld.12.0351
Riza, A. L., Pearson, F., Ugarte-Gil, C., Alisjahbana, B., van de Vijver, S., Panduru, N. M., et al. (2014). Clinical management of concurrent diabetes and tuberculosis and the implications for patient services. Lancet Diabetes Endocrinol, 2(9), 740-753. doi:10.1016/S2213-8587(14)70110-X
Schiff, M. H. (2000). Role of interleukin 1 and interleukin 1 receptor antagonist in the mediation of rheumatoid arthritis. Ann Rheum Dis, 59 Suppl 1, i103-108.
Schnappinger, D., Ehrt, S., Voskuil, M. I., Liu, Y., Mangan, J. A., Monahan, I. M., et al. (2003). Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages: Insights into the Phagosomal Environment. J Exp Med, 198(5), 693-704. doi:10.1084/jem.20030846
Schroder, K., & Tschopp, J. (2010). The inflammasomes. Cell, 140(6), 821-832.
Seddon, J., Kasprowicz, V., Walker, N. F., Yuen, H. M., Sunpath, H., Tezera, L., et al. (2013). Procollagen III N-terminal propeptide and desmosine are released by matrix destruction in pulmonary tuberculosis. J Infect Dis, 208(10), 1571-1579. doi:10.1093/infdis/jit343
Shapiro, S. D., Goldstein, N. M., Houghton, A. M., Kobayashi, D. K., Kelley, D., & Belaaouaj, A. (2003). Neutrophil elastase contributes to cigarette smoke-induced emphysema in mice. Am J Pathol, 163(6), 2329-2335. doi:10.1016/S0002-9440(10)63589-4
Singhal, A., Jie, L., Kumar, P., Hong, G. S., Leow, M. K., Paleja, B., et al. (2014). Metformin as adjunct antituberculosis therapy. Sci Transl Med, 6(263), 263ra159. doi:10.1126/scitranslmed.3009885
Stinear, T. P., Seemann, T., Harrison, P. F., Jenkin, G. A., Davies, J. K., Johnson, P. D., et al. (2008). Insights from the complete genome sequence of Mycobacterium marinum on the evolution of Mycobacterium tuberculosis. Genome Res, 18(5), 729-741. doi:10.1101/gr.075069.107
Su, W. J., Feng, J. Y., Chiu, Y. C., Huang, S. F., & Lee, Y. C. (2011). Role of 2-month sputum smears in predicting culture conversion in pulmonary tuberculosis. Eur Respir J, 37(2), 376-383. doi:10.1183/09031936.00007410
Taiwan National Infectious Disease Statistics System. (2016). Taiwan Centers for Disease Control Retrieved from http://nidss.cdc.gov.tw/en/.
Takahashi, H., Nukiwa, T., Yoshimura, K., Quick, C. D., States, D. J., Holmes, M. D., et al. (1988). Structure of the human neutrophil elastase gene. J Biol Chem, 263(29), 14739-14747.
Tan, K. S., Lee, K. O., Low, K. C., Gamage, A. M., Liu, Y., Tan, G. Y., et al. (2012). Glutathione deficiency in type 2 diabetes impairs cytokine responses and control of intracellular bacteria. J Clin Invest, 122(6), 2289-2300. doi:10.1172/JCI57817
Tschopp, J., & Schroder, K. (2010). NLRP3 inflammasome activation: The convergence of multiple signalling pathways on ROS production? Nat Rev Immunol, 10(3), 210-215. doi:10.1038/nri2725
Ugarte-Gil, C. A., Elkington, P., Gilman, R. H., Coronel, J., Tezera, L. B., Bernabe-Ortiz, A., et al. (2013). Induced sputum MMP-1, -3 & -8 concentrations during treatment of tuberculosis. PLoS One, 8(4), e61333. doi:10.1371/journal.pone.0061333
Vallerskog, T., Martens, G. W., & Kornfeld, H. (2010). Diabetic mice display a delayed adaptive immune response to Mycobacterium tuberculosis. J Immunol, 184(11), 6275-6282. doi:10.4049/jimmunol.1000304
Verrall, A. J., Netea, M. G., Alisjahbana, B., Hill, P. C., & van Crevel, R. (2014). Early clearance of Mycobacterium tuberculosis: a new frontier in prevention. Immunology, 141(4), 506-513.
Vesosky, B., Rottinghaus, E. K., Stromberg, P., Turner, J., & Beamer, G. (2010). CCL5 participates in early protection against Mycobacterium tuberculosis. J Leukoc Biol, 87(6), 1153-1165. doi:10.1189/jlb.1109742
Wallis, R. S., & Hafner, R. (2015). Advancing host-directed therapy for tuberculosis. Nat Rev Immunol, 15(4), 255-263. doi:10.1038/nri3813
Wallis, R. S., Maeurer, M., Mwaba, P., Chakaya, J., Rustomjee, R., Migliori, G. B., et al. (2016). Tuberculosis-advances in development of new drugs, treatment regimens, host-directed therapies, and biomarkers. Lancet Infect Dis, 16(4), e34-46. doi:10.1016/S1473-3099(16)00070-0
Wang, W. Z. (2010). Lack of Reactive Oxygen Species Alters the Lung Inflammation to Mycobacterium bovis (BCG) Infection in a CGD Mouse Model. (Master's thesis), National Cheng Kung University
Weinrauch, Y., Drujan, D., Shapiro, S. D., Weiss, J., & Zychlinsky, A. (2002). Neutrophil elastase targets virulence factors of enterobacteria. Nature, 417(6884), 91-94. doi:10.1038/417091a
Williams, G. T., & Williams, W. J. (1983). Granulomatous inflammation--a review. J Clin Pathol, 36(7), 723-733.
Yen, C. L. (2007). The influence of diabetes mellitus on the innate immune responses in pulmonary tuberculosis patients. (Master's thesis), National Cheng Kung University.
Yen, Y. T., Wu, M. H., Lai, W. W., Chang, J. M., Hsu, I. L., Chen, Y. Y., et al. (2013). The role of video-assisted thoracoscopic surgery in therapeutic lung resection for pulmonary tuberculosis. Ann Thorac Surg, 95(1), 257-263. doi:10.1016/j.athoracsur.2012.09.034
Zumla, A., Maeurer, M., Host-Directed Therapies, N., Chakaya, J., Hoelscher, M., Ntoumi, F., et al. (2015). Towards host-directed therapies for tuberculosis. Nat Rev Drug Discov, 14(8), 511-512. doi:10.1038/nrd4696

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