CoChat
Sign Up
Cited by 113Tuberculosis Research and EpidemiologyImmune responses and vaccinationsInfectious Diseases and Tuberculosis

Mycobacterium tuberculosis Infection-Driven Foamy Macrophages and Their Implications in Tuberculosis Control as Targets for Host-Directed Therapy

Open access
Shim, Dahee, Kim, Hagyu, Shin, Sung Jae·2020·Frontiers in Immunology
DOI 10.3389/fimmu.2020.00910PMC PMC7235167
Open this paper in CoChat — free accountOpen PDF

Abstract

Tuberculosis (TB) is a leading cause of death worldwide following infection with Mycobacterium tuberculosis (Mtb), with 1.5 million deaths from this disease reported in 2018. Once the bacilli are inhaled, alveolar and interstitial macrophages become infected with Mtb and differentiate into lipid-laden foamy macrophages leading to lung inflammation. Thus, the presence of lipid-laden foamy macrophages is the hallmark of TB granuloma; these Mtb-infected foamy macrophages are the major niche for Mtb survival. The fate of TB pathogenesis is likely determined by the altered function of Mtb-infected macrophages, which initiate and mediate TB-related lung inflammation. As Mtb-infected foamy macrophages play central roles in the pathogenesis of Mtb, they may be important in the development of host-directed therapy against TB. Here, we summarize and discuss the current understanding of the alterations in alveolar and interstitial macrophages in the regulation of Mtb infection-induced immune responses. Metabolic reprogramming of lipid-laden foamy macrophages following Mtb infection or virulence factors are also summarized. Furthermore, we review the therapeutic interventions targeting immune responses and metabolic pathways, from in vitro, in vivo, and clinical studies. This review will further our understanding of the Mtb-infected foamy macrophages, which are both the major Mtb niche and therapeutic targets against TB.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fimmu.2020.00910

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 91

  1. [1]The Lancet End the tuberculosis emergency: a promise is not enough. Lancet. (2019) 394: 1482 10.1016/S0140-6736(19)32459-6 31657723 · DOI
  2. [2]Cohen SB Gern BH Delahaye JL Adams KN Plumlee CR Winkler JK. Alveolar macrophages provide an early Mycobacterium tuberculosis niche and initiate dissemination. Cell Host Microbe. (2018) 24: 439– 46.e4. 10.1016/j.chom.2018.08.001 30146391 PMC6152889 · DOI
  3. [3]Bussi C Gutierrez MG. Mycobacterium tuberculosis infection of host cells in space and time. FEMS Microbiol Rev. (2019) 43: 341– 61. 10.1093/femsre/fuz006 30916769 PMC6606852 · DOI
  4. [4]Meena LS Rajni. Survival mechanisms of pathogenic Mycobacterium tuberculosis H37Rv. FEBS J. (2010) 277: 2416– 27. 10.1111/j.1742-4658.2010.07666.x 20553485 · DOI
  5. [5]Ehlers S Schaible UE. The granuloma in tuberculosis: dynamics of a host-pathogen collusion. Front Immunol. (2012) 3: 411. 10.3389/fimmu.2012.00411 23308075 PMC3538277 · DOI
  6. [6]Orme IM Basaraba RJ. The formation of the granuloma in tuberculosis infection. Semin Immunol. (2014) 26: 601– 9. 10.1016/j.smim.2014.09.009 25453231 · DOI
  7. [7]Cadena AM Fortune SM Flynn JL. Heterogeneity in tuberculosis. Nat Rev Immunol. (2017) 17: 691– 702. 10.1038/nri.2017.69 28736436 PMC6247113 · DOI
  8. [8]Russell DG Cardona PJ Kim MJ Allain S Altare F. Foamy macrophages and the progression of the human tuberculosis granuloma. Nat Immunolgy. (2009) 10: 943– 8. 10.1038/ni.1781 19692995 PMC2759071 · DOI
  9. [9]Ramakrishnan L. Revisiting the role of the granuloma in tuberculosis. Nat Rev Immunol. (2012) 12: 352– 66. 10.1038/nri3211 22517424 · DOI
  10. [10]Guerrini V Prideaux B Blanc L Bruiners N Arrigucci R Singh S. Storage lipid studies in tuberculosis reveal that foam cell biogenesis is disease-specific. PLoS Pathog. (2018) 14: e1007223. 10.1371/journal.ppat.1007223 30161232 PMC6117085 · DOI
  11. [11]McClean CM Tobin DM. Macrophage form, function, and phenotype in mycobacterial infection: lessons from tuberculosis and other diseases. Pathog Dis. (2016) 74: ftw068. 10.1093/femspd/ftw068 27402783 PMC5985490 · DOI
  12. [12]Gentek R Molawi K Sieweke MH. Tissue macrophage identity and self-renewal. Immunol Rev. (2014) 262: 56– 73. 10.1111/imr.12224 25319327 · DOI
  13. [13]Ginhoux F Guilliams M. Tissue-Resident macrophage ontogeny and homeostasis. Immunity. (2016) 44: 439– 49. 10.1016/j.immuni.2016.02.024 26982352 · DOI · Paper page
  14. [14]Ginhoux F Schultze JL Murray PJ Ochando J Biswas SK. New insights into the multidimensional concept of macrophage ontogeny, activation and function. Nat Immunol. (2016) 17: 34– 40. 10.1038/ni.3324 26681460 · DOI
  15. [15]Tan SY Krasnow MA. Developmental origin of lung macrophage diversity. Development. (2016) 143: 1318– 27. 10.1242/dev.129122 26952982 PMC4852511 · DOI
  16. [16]Malur A McCoy AJ Arce S Barna BP Kavuru MS Malur AG. Deletion of PPAR gamma in alveolar macrophages is associated with a Th-1 pulmonary inflammatory response. J Immunol. (2009) 182: 5816– 22. 10.4049/jimmunol.0803504 19380830 · DOI
  17. [17]Hussell T Bell TJ. Alveolar macrophages: plasticity in a tissue-specific context. Nat Rev Immunol. (2014) 14: 81– 93. 10.1038/nri3600 24445666 · DOI · Paper page
  18. [18]Schneider C Nobs SP Kurrer M Rehrauer H Thiele C Kopf M. Induction of the nuclear receptor PPAR-gamma by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages. Nat Immunol. (2014) 15: 1026– 37. 10.1038/ni.3005 25263125 · DOI
  19. [19]Guilliams M De Kleer I Henri S Post S Vanhoutte L De Prijck S. Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF. J Exp Med. (2013) 210: 1977– 92. 10.1084/jem.20131199 24043763 PMC3782041 · DOI
  20. [20]Gosselin D Link VM Romanoski CE Fonseca GJ Eichenfield DZ Spann NJ. Environment drives selection and function of enhancers controlling tissue-specific macrophage identities. Cell. (2014) 159: 1327– 40. 10.1016/j.cell.2014.11.023 25480297 PMC4364385 · DOI · Paper page
  21. [21]Lavin Y Winter D Blecher-Gonen R David E Keren-Shaul H Merad M. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell. (2014) 159: 1312– 26. 10.1016/j.cell.2014.11.018 25480296 PMC4437213 · DOI · Paper page
  22. [23]Allard B Panariti A Martin JG. Alveolar macrophages in the resolution of inflammation, tissue repair, and tolerance to infection. Front Immunol. (2018) 9: 1777. 10.3389/fimmu.2018.01777 30108592 PMC6079255 · DOI
  23. [24]Fathi M Johansson A Lundborg M Orre L Skold CM Camner P. Functional and morphological differences between human alveolar and interstitial macrophages. Exp Mol Pathol. (2001) 70: 77– 82. 10.1006/exmp.2000.2344 11263950 · DOI
  24. [25]Yu YR O'Koren EG Hotten DF Kan MJ Kopin D Nelson ER. A Protocol for the comprehensive flow cytometric analysis of immune cells in normal and inflamed murine non-lymphoid tissues. PLoS ONE. (2016) 11: e0150606. 10.1371/journal.pone.0150606 26938654 PMC4777539 · DOI
  25. [26]Gibbings SL Thomas SM Atif SM McCubbrey AL Desch AN Danhorn T. Three unique interstitial macrophages in the murine lung at steady state. Am J Respir Cell Mol Biol. (2017) 57: 66– 76. 10.1165/rcmb.2016-0361OC 28257233 PMC5516280 · DOI
  26. [28]Ley K. M1 Means Kill; M2 Means Heal. J Immunol. (2017) 199: 2191– 3. 10.4049/jimmunol.1701135 28923980 · DOI
  27. [29]Orecchioni M Ghosheh Y Pramod AB Ley K. Macrophage polarization: different gene signatures in M1(LPS+) vs. classically and M2(LPS-) vs. alternatively activated macrophages. Front Immunol. (2019) 10: 1084. 10.3389/fimmu.2019.01084 31178859 PMC6543837 · DOI · Paper page
  28. [30]Hume DA. Macrophages as APC and the dendritic cell myth. J Immunol. (2008) 181: 5829– 35. 10.4049/jimmunol.181.9.5829 18941170 · DOI
  29. [31]Murray PJ. Macrophage polarization. Ann Rev Physiol. (2017) 79: 541– 66. 10.1146/annurev-physiol-022516-034339 27813830 · DOI · Paper page
  30. [32]O'Neill LA Kishton RJ Rathmell J. A guide to immunometabolism for immunologists. Nat Rev Immunol. (2016) 16: 553– 65. 10.1038/nri.2016.70 27396447 PMC5001910 · DOI · Paper page
  31. [33]Wculek SK Khouili SC Priego E Heras-Murillo I Sancho D. Metabolic control of dendritic cell functions: digesting information. Front Immunol. (2019) 10: 775. 10.3389/fimmu.2019.00775 31073300 PMC6496459 · DOI
  32. [34]Cameron AM Castoldi A Sanin DE Flachsmann LJ Field CS Puleston DJ. Inflammatory macrophage dependence on NAD(+) salvage is a consequence of reactive oxygen species-mediated DNA damage. Nat Immunol. (2019) 20: 420– 32. 10.1038/s41590-019-0336-y 30858618 PMC12842115 · DOI · Paper page
  33. [35]Feingold KR Shigenaga JK Kazemi MR McDonald CM Patzek SM Cross AS. Mechanisms of triglyceride accumulation in activated macrophages. J Leukoc Biol. (2012) 92: 829– 39. 10.1189/jlb.1111537 22753953 PMC3441312 · DOI
  34. [36]Watanabe S Alexander M Misharin AV Budinger GRS. The role of macrophages in the resolution of inflammation. J Clin Invest. (2019) 129: 2619– 28. 10.1172/JCI124615 31107246 PMC6597225 · DOI · Paper page
  35. [37]Russell DG Huang L VanderVen BC. Immunometabolism at the interface between macrophages and pathogens. Nat Rev Immunol. (2019) 19: 291– 304. 10.1038/s41577-019-0124-9 30679807 PMC7032560 · DOI
  36. [38]Puleston DJ Buck MD Klein Geltink RI Kyle RL Caputa G O'Sullivan D. Polyamines and eIF5A hypusination modulate mitochondrial respiration and macrophage activation. Cell Metab. (2019) 30: 352– 63.e8. 10.1016/j.cmet.2019.05.003 31130465 PMC6688828 · DOI
  37. [39]Huang L Nazarova EV Tan S Liu Y Russell DG. Growth of Mycobacterium tuberculosis in vivo segregates with host macrophage metabolism and ontogeny. J Exp Med. (2018) 215: 1135– 52. 10.1084/jem.20172020 29500179 PMC5881470 · DOI
  38. [40]Pisu D Huang L Grenier JK Russell DG. Dual RNA-Seq of Mtb-infected macrophages in vivo reveals ontologically distinct host-pathogen interactions. Cell Rep. (2020) 30: 335– 50.e4. 10.1016/j.celrep.2019.12.033 31940480 PMC7032562 · DOI
  39. [41]Rothchild AC Olson GS Nemeth J Amon LM Mai D Gold ES. Alveolar macrophages generate a noncanonical NRF2-driven transcriptional response to Mycobacterium tuberculosis in vivo. Sci Immunol. (2019) 4: eaaw6693. 10.1126/sciimmunol.aaw6693 31350281 PMC6910245 · DOI
  40. [42]Huang Z Luo Q Guo Y Chen J Xiong G Peng Y. Mycobacterium tuberculosis-induced polarization of human macrophage orchestrates the formation and development of tuberculous granulomas in vitro. PLoS ONE. (2015) 10: e0129744. 10.1371/journal.pone.0129744 26091535 PMC4474964 · DOI
  41. [43]Refai A Gritli S Barbouche MR Essafi M. Mycobacterium tuberculosis virulent factor ESAT-6 drives macrophage differentiation toward the pro-inflammatory M1 phenotype and subsequently switches it to the anti-inflammatory M2 phenotype. Front Cell Infect Microbiol. (2018) 8: 327. 10.3389/fcimb.2018.00327 30283745 PMC6157333 · DOI
  42. [44]van der Wel N Hava D Houben D Fluitsma D van Zon M Pierson J. M. tuberculosis and M. leprae translocate from the phagolysosome to the cytosol in myeloid cells. Cell. (2007) 129: 1287– 98. 10.1016/j.cell.2007.05.059 17604718 · DOI · Paper page
  43. [45]Davis JM Ramakrishnan L. The role of the granuloma in expansion and dissemination of early tuberculous infection. Cell. (2009) 136: 37– 49. 10.1016/j.cell.2008.11.014 19135887 PMC3134310 · DOI
  44. [46]Huang SC Everts B Ivanova Y O'Sullivan D Nascimento M Smith AM. Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nat Immunol. (2014) 15: 846– 55. 10.1038/ni.2956 25086775 PMC4139419 · DOI
  45. [47]Mayer-Barber KD Andrade BB Oland SD Amaral EP Barber DL Gonzales J. Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk. Nature. (2014) 511: 99– 103. 10.1038/nature13489 24990750 PMC4809146 · DOI
  46. [48]Shi L Salamon H Eugenin EA Pine R Cooper A Gennaro ML. Infection with Mycobacterium tuberculosis induces the Warburg effect in mouse lungs. Sci Rep. (2015) 5: 18176. 10.1038/srep18176 26658723 PMC4674750 · DOI
  47. [49]Braverman J Sogi KM Benjamin D Nomura DK Stanley SA. HIF-1α Is an essential mediator of IFN-γ-dependent immunity to Mycobacterium tuberculosis. J Immunol. (2016) 197: 1287– 97. 10.4049/jimmunol.1600266 27430718 PMC4976004 · DOI
  48. [50]Cooper AM Solache A Khader SA. Interleukin-12 and tuberculosis: an old story revisited. Curr Opin Immunol. (2007) 19: 441– 7. 10.1016/j.coi.2007.07.004 17702558 PMC2075090 · DOI
  49. [51]Abdalla AE Lambert N Duan X Xie J. Interleukin-10 family and tuberculosis: an old story renewed. Int J Biol Sci. (2016) 12: 710– 7. 10.7150/ijbs.13881 27194948 PMC4870714 · DOI
  50. [52]Warsinske HC Pienaar E Linderman JJ Mattila JT Kirschner DE. Deletion of TGF-β1 increases bacterial clearance by cytotoxic T cells in a tuberculosis granuloma model. Front Immunol. (2017) 8: 1843. 10.3389/fimmu.2017.01843 29326718 PMC5742530 · DOI
  51. [53]Mori M Itabe H Higashi Y Fujimoto Y Shiomi M Yoshizumi M. Foam cell formation containing lipid droplets enriched with free cholesterol by hyperlipidemic serum. J Lipid Res. (2001) 42: 1771– 81. 11714846
  52. [54]Ordway D Henao-Tamayo M Orme IM Gonzalez-Juarrero M. Foamy macrophages within lung granulomas of mice infected with Mycobacterium tuberculosis express molecules characteristic of dendritic cells and antiapoptotic markers of the TNF receptor-associated factor family. J Immunol. (2005) 175: 3873– 81. 10.4049/jimmunol.175.6.3873 16148133 · DOI
  53. [55]Ríos-Barrera VA Campos-Peña V Aguilar-León D Lascurain LR Meraz-Ríos MA Moreno J. Macrophage and T lymphocyte apoptosis during experimental pulmonary tuberculosis: their relationship to mycobacterial virulence. Eur J Immunol. (2006) 36: 345– 53. 10.1002/eji.200535202 16421947 · DOI
  54. [56]Nabeshima S Nomoto M Matsuzaki G Kishihara K Taniguchi H Yoshida S. T-Cell hyporesponsiveness induced by activated macrophages through nitric oxide production in mice infected with Mycobacterium tuberculosis. Infect Immun. (1999) 67: 3221– 6. 10.1128/IAI.67.7.3221-3226.1999 10377094 PMC116499 · DOI
  55. [57]Hernandez-Pando R Orozco H Arriaga K Sampieri A Larriva-Sahd J Madrid-Marina V. Analysis of the local kinetics and localization of interleukin-1 alpha, tumour necrosis factor-alpha and transforming growth factor-beta, during the course of experimental pulmonary tuberculosis. Immunology. (1997) 90: 607– 17. 10.1046/j.1365-2567.1997.00193.x 9176116 PMC1456699 · DOI
  56. [58]Peyron P Vaubourgeix J Poquet Y Levillain F Botanch C Bardou F. Foamy macrophages from tuberculous patients' granulomas constitute a nutrient-rich reservoir for M. tuberculosis persistence. PLoS Pathog. (2008) 4: e1000204. 10.1371/journal.ppat.1000204 19002241 PMC2575403 · DOI · Paper page
  57. [59]Roque NR Lage SL Navarro R Fazolini N Maya-Monteiro CM Rietdorf J Rab7 controls lipid droplet-phagosome association during mycobacterial infection. Biochim Biophys Acta Mol Cell Biol Lipids. (2020) 1865: 158703 10.1016/j.bbalip.2020.158703 32229179 · DOI
  58. [60]Munoz-Elias EJ Upton AM Cherian J McKinney JD. Role of the methylcitrate cycle in Mycobacterium tuberculosis metabolism, intracellular growth, and virulence. Mol Microbiol. (2006) 60: 1109– 22. 10.1111/j.1365-2958.2006.05155.x 16689789 · DOI
  59. [61]Nazarova EV Montague CR La T Wilburn KM Sukumar N Lee W. Rv3723/LucA coordinates fatty acid and cholesterol uptake in Mycobacterium tuberculosis. ELife. (2017) 6: e26969. 10.7554/eLife.26969.019 28708968 PMC5487216 · DOI
  60. [62]Nazarova EV Montague CR Huang L La T Russell D VanderVen BC. The genetic requirements of fatty acid import by Mycobacterium tuberculosis within macrophages. ELife. (2019) 8: e43621. 10.7554/eLife.43621.015 30735132 PMC6368401 · DOI
  61. [63]Singh KH Jha B Dwivedy A Choudhary E N AG Ashraf A. Characterization of a secretory hydrolase from Mycobacterium tuberculosis sheds critical insight into host lipid utilization by M. tuberculosis. J Biol Chem. (2017) 292: 11326– 35. 10.1074/jbc.M117.794297 28515317 PMC5500798 · DOI
  62. [64]Tong J Liu Q Wu J Jiang Y Takiff HE Gao Q. Mycobacterium tuberculosis strains of the modern Beijing sublineage excessively accumulate triacylglycerols in vitro. Tuberculosis. (2019) 120: 101892. 10.1016/j.tube.2019.101892 31783320 · DOI
  63. [65]Baek SH Li AH Sassetti CM. Metabolic regulation of mycobacterial growth and antibiotic sensitivity. PLoS Biol. (2011) 9: e1001065. 10.1371/journal.pbio.1001065 21629732 PMC3101192 · DOI · Paper page
  64. [66]Rodriguez JG Hernandez AC Helguera-Repetto C Aguilar Ayala D Guadarrama-Medina R Anzola JM. Global adaptation to a lipid environment triggers the dormancy-related phenotype of Mycobacterium tuberculosis. mBio. (2014) 5: e01125– 14. 10.1128/mBio.01125-14 24846381 PMC4030484 · DOI
  65. [67]Jaisinghani N Dawa S Singh K Nandy A Menon D Bhandari PD. Necrosis driven triglyceride synthesis primes macrophages for inflammation during Mycobacterium tuberculosis infection. Front Immunol. (2018) 9: 1490. 10.3389/fimmu.2018.01490 30018616 PMC6037689 · DOI
  66. [68]Daniel J Maamar H Deb C Sirakova TD Kolattukudy PE. Mycobacterium tuberculosis uses host triacylglycerol to accumulate lipid droplets and acquires a dormancy-like phenotype in lipid-loaded macrophages. PLoS Pathog. (2011) 7: e1002093. 10.1371/journal.ppat.1002093 21731490 PMC3121879 · DOI
  67. [69]Singh V Kaur C Chaudhary VK Rao KV Chatterjee S. M. tuberculosis secretory protein ESAT-6 induces metabolic flux perturbations to drive foamy macrophage differentiation. Sci Rep. (2015) 5: 12906. 10.1038/srep12906 26250836 PMC5388048 · DOI
  68. [70]Singh V Jamwal S Jain R Verma P Gokhale R Rao KV. Mycobacterium tuberculosis-driven targeted recalibration of macrophage lipid homeostasis promotes the foamy phenotype. Cell Host Microbe. (2012) 12: 669– 81. 10.1016/j.chom.2012.09.012 23159056 · DOI · Paper page
  69. [71]Mahajan S Dkhar HK Chandra V Dave S Nanduri R Janmeja AK. Mycobacterium tuberculosis modulates macrophage lipid-sensing nuclear receptors PPARgamma and TR4 for survival. J Immunol. (2012) 188: 5593– 603. 10.4049/jimmunol.1103038 22544925 · DOI
  70. [72]Arnett E Weaver AM Woodyard KC Montoya MJ Li M Hoang KV. PPARγ is critical for Mycobacterium tuberculosis induction of Mcl-1 and limitation of human macrophage apoptosis. PLoS Pathog. (2018) 14: e1007100. 10.1371/journal.ppat.1007100 29928066 PMC6013021 · DOI
  71. [73]Kim YS Lee HM Kim JK Yang CS Kim TS Jung M. PPAR-α activation mediates innate host defense through induction of TFEB and lipid catabolism. J Immunol. (2017) 198: 3283– 95. 10.4049/jimmunol.1601920 28275133 · DOI
  72. [74]Korf H Vander Beken S Romano M Steffensen KR Stijlemans B Gustafsson JA. Liver X receptors contribute to the protective immune response against Mycobacterium tuberculosis in mice. J Clin Invest. (2009) 119: 1626– 37. 10.1172/JCI35288 19436111 PMC2689129 · DOI
  73. [75]Ahsan F Maertzdorf J Guhlich-Bornhof U Kaufmann SHE Moura-Alves P. IL-36/LXR axis modulates cholesterol metabolism and immune defense to Mycobacterium tuberculosis. Sci Rep. (2018) 8: 1520. 10.1038/s41598-018-19476-x 29367626 PMC5784124 · DOI
  74. [76]Ouimet M Koster S Sakowski E Ramkhelawon B van Solingen C Oldebeken S. Mycobacterium tuberculosis induces the miR-33 locus to reprogram autophagy and host lipid metabolism. Nat Immunol. (2016) 17: 677– 86. 10.1038/ni.3434 27089382 PMC4873392 · DOI
  75. [77]Martens GW Arikan MC Lee J Ren F Vallerskog T Kornfeld H. Hypercholesterolemia impairs immunity to tuberculosis. Infect Immun. (2008) 76: 3464– 72. 10.1128/IAI.00037-08 18505807 PMC2493195 · DOI
  76. [78]Vrieling F Wilson L Rensen PCN Walzl G Ottenhoff THM Joosten SA. Oxidized low-density lipoprotein (oxLDL) supports Mycobacterium tuberculosis survival in macrophages by inducing lysosomal dysfunction. PLoS Pathog. (2019) 15: e1007724. 10.1371/journal.ppat.1007724 30998773 PMC6490946 · DOI
  77. [79]Dutta NK Bruiners N Pinn ML Zimmerman MD Prideaux B Dartois V. Statin adjunctive therapy shortens the duration of TB treatment in mice. J Antimicrob Chemother. (2016) 71: 1570– 7. 10.1093/jac/dkw014 26903278 PMC5007636 · DOI
  78. [80]Kang YA Choi NK Seong JM Heo EY Koo BK Hwang SS. The effects of statin use on the development of tuberculosis among patients with diabetes mellitus. Int J Tuberc Lung Dis. (2014) 18: 717– 24. 10.5588/ijtld.13.0854 24903944 · DOI
  79. [81]Chen YT Kuo SC Chao PW Chang YY Use of lipid-lowering agents is not associated with improved outcomes for tuberculosis patients on standard-course therapy: a population-based cohort study. PLoS ONE. (2019) 14: e0210479 10.1371/journal.pone.0210479 30633771 PMC6329498 · DOI
  80. [82]Skerry C Pinn ML Bruiners N Pine R Gennaro ML Karakousis PC. Simvastatin increases the in vivo activity of the first-line tuberculosis regimen. J Antimicrob Chemother. (2014) 69: 2453– 7. 10.1093/jac/dku166 24855121 PMC4184365 · DOI
  81. [83]Lai CC Lee MT Lee SH Hsu WT Chang SS Chen SC. Statin treatment is associated with a decreased risk of active tuberculosis: an analysis of a nationally representative cohort. Thorax. (2016) 71: 646– 51. 10.1136/thoraxjnl-2015-207052 26941271 · DOI
  82. [84]Kapoor N Pawar S Sirakova TD Deb C Warren WL Kolattukudy PE. Human granuloma in vitro model, for TB dormancy and resuscitation. PLoS ONE. (2013) 8: e53657. 10.1371/journal.pone.0053657 23308269 PMC3538642 · DOI
  83. [85]Fonseca KL Rodrigues PNS Olsson IAS Saraiva M. Experimental study of tuberculosis: from animal models to complex cell systems and organoids. PLoS Pathog. (2017) 13: e1006421. 10.1371/journal.ppat.1006421 28817682 PMC5560521 · DOI
  84. [86]Elkington P Lerm M Kapoor N Mahon R Pienaar E Huh D. In vitro granuloma models of tuberculosis: potential and challenges. J Infect Dis. (2019) 219: 1858– 66. 10.1093/infdis/jiz020 30929010 PMC6534193 · DOI
  85. [87]Blanc L Daudelin IB Podell BK Chen PY Zimmerman M Martinot AJ. High-resolution mapping of fluoroquinolones in TB rabbit lesions reveals specific distribution in immune cell types. ELife. (2018) 7: e41115. 10.7554/eLife.41115.025 30427309 PMC6249001 · DOI
  86. [88]Tseng CH. Metformin decreases risk of tuberculosis infection in type 2 diabetes patients. J Clin Med. (2018) 7: 264. 10.3390/jcm7090264 30205606 PMC6162822 · DOI
  87. [89]Lin SY Tu HP Lu PL Chen TC Wang WH Chong IW. Metformin is associated with a lower risk of active tuberculosis in patients with type 2 diabetes. Respirology. (2018) 23: 1063– 73. 10.1111/resp.13338 29943489 · DOI
  88. [90]Zhang M He JQ. Impacts of metformin on tuberculosis incidence and clinical outcomes in patients with diabetes: a systematic review and meta-analysis. Eur J Clin Pharmacol. (2019) 76: 149– 59. 10.1007/s00228-019-02786-y 31786617 · DOI
  89. [91]Mehrotra P Jamwal SV Saquib N Sinha N Siddiqui Z Manivel V. Pathogenicity of Mycobacterium tuberculosis is expressed by regulating metabolic thresholds of the host macrophage. PLoS Pathog. (2014) 10: e1004265. 10.1371/journal.ppat.1004265 25058590 PMC4110042 · DOI
  90. [92]Coriat R Mir O Ropert S Loulergue P Billemont B Goldwasser F. Reactivation of tuberculosis during temsirolimus therapy. Invest New Drugs. (2011) 29: 1494– 6. 10.1007/s10637-010-9487-2 20623161 · DOI
  91. [93]Jeon SY Yhim HY Lee NR Song EK Kwak JY Yim CY. Everolimus-induced activation of latent Mycobacterium tuberculosis infection in a patient with metastatic renal cell carcinoma. Korean J Intern Med. (2017) 32: 365– 8. 10.3904/kjim.2015.121 26837008 PMC5339459 · DOI

Cited by

Sorted by citations

Authors
Shim, D., Kim, H., & Shin, S. J.
Affiliations
Yonsei University (KR)
Corresponding author
Shin, Sung Jae
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2020-05-12
Volume
11
Pages
1601-1601
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2020.00910
PMC
PMC7235167
OpenAlex
W3024548582
Cited by
113
References
2
Citations by year
2026: 15 · 2025: 22 · 2024: 17 · 2023: 17 · 2022: 21 · 2021: 17 · 2020: 2 · 2019: 1
FWCI
0.67
Type
journal article
Language
en
Update notices
corrigendum (2020-07-17)
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Research Foundation of Korea
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
  • Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
Keywords
Mycobacterium tuberculosis, tuberculosis, foam cells, lipid-laden macrophages, host-directed therapy, granuloma, alveolar macrophages, interstitial macrophages, macrophage metabolic reprogramming, lung inflammation, tuberculosis pathogenesis, therapeutic target
MeSH terms
Animals, Foam Cells, Humans, Inflammation, Mycobacterium tuberculosis, Tuberculosis, Macrophages, Alveolar, Mice, Host-Pathogen Interactions, Cellular Reprogramming

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review