Exposure to particulate matter pollutant PM2.5 diminishes the immune response to mycobacterial antigens relevant to contain the infection in the granuloma, thus leading to reactivation of latent bacilli. The present study was therefore designed based on the hypothesis that exposure to PM2.5 affects the granuloma formation and reactivation of latent mycobacterial bacilli contained in the granuloma. For the sampling of PM2.5, based on initial standardisations, Teflon filter was selected over the quartz filter. Two different approaches were used to study the effect of PM2.5 on the human PBMC granuloma formed by Mycobacterium bovis BCG at multiplicity of infection (MOI) 0.1. In the first approach, granuloma formed in the presence of PM2.5 was loosely packed and ill-defined with significant downregulation of dormancy-associated mycobacterial genes, upregulation of reactivation-associated rpfB gene along with a significant increase in TNFα level without any change in the bacterial load in terms of CFUs. In the second approach, preformed human PBMC granuloma using M. bovis BCG was treated with PM2.5 that resulted in the disruption of granuloma architecture along with downregulation of not only dormancy-associated genes but also reactivation-associated rpfB gene of mycobacterial bacilli recovered from granuloma. However, there was no significant change in the host cytokine levels. Therefore, it can be inferred that PM2.5 can modulate the granuloma formation in vitro as well as mycobacterial gene expression in the granuloma with a possible role in the reactivation of latent bacilli.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
All data generated or analysed during this study are included in this published article (and its supplementary information files).
Abhishek S, Saikia UN, Gupta A et al (2018) Transcriptional profile of Mycobacterium tuberculosis in an in vitro model of intraocular tuberculosis. Front Cell Infect Microbiol 8:330. https://doi.org/10.3389/fcimb.2018.00330
Ding R, Jin Y, Liu X et al (2017) Dose- and time-effect responses of DNA methylation and histone H3K9 acetylation changes induced by traffic-related air pollution. Sci Rep 3:43737. https://doi.org/10.1038/srep43737
Du P, Sohaskey CD, Shi L (2016) Transcriptional and physiological changes during Mycobacterium tuberculosis reactivation from non-replicating persistence. Front Microbiol 7:1346. https://doi.org/10.3389/fmicb.2016.01346
Ge E, Fan M, Qiu H et al (2017) Ambient sulfur dioxide levels associated with reduced risk of initial outpatient visits for tuberculosis: a population based time series analysis. Environ Pollut 228:408–415. https://doi.org/10.1016/j.envpol.2017.05.051
Gideon HP, Flynn JL (2011) Latent tuberculosis: what the host “sees”? Immunol Res 50(2–3):202–212. https://doi.org/10.1007/s12026-011-8229-7
Hu Y, Movahedzadeh F, Stoker NG, Coates ARM (2006) Deletion of the Mycobacterium tuberculosis α-crystallin-like HspX gene causes increased bacterial growth in vivo. Infect Immun 74:861–868. https://doi.org/10.1128/IAI.74.2.861-868.2006
Ibironke O, Carranza C, Sarkar S et al (2019) Urban Air pollution particulates suppress human T-cell response to Mycobacterium tuberculosis. Int J Environ Res Public Health 16(21):4112. https://doi.org/10.3390/ijerph16214112
Islamoglu H, Cao R, Teskey G et al (2018) Effects of ReadiSorb L-GSH in altering granulomatous responses against Mycobacterium tuberculosis infection. J Clin Med 7:40. https://doi.org/10.3390/jcm7030040
Kana BD, Gordhan BG, Downing KJ et al (2008) The resuscitation-promoting factors of Mycobacterium tuberculosis are required for virulence and resuscitation from dormancy but are collectively dispensable for growth in vitro. Mol Microbiol 67:672–684. https://doi.org/10.1111/j.1365-2958.2007.06078.x
Kapoor N, Pawar S, Sirakova TD, Deb C, Warren WL, Kolattukudy PE (2013) Human granuloma in vitro model, for TB dormancy and resuscitation. PLoS ONE 8:e53657. https://doi.org/10.1371/journal.pone.0053657
Kinger AK, Tyagi JS (1993) Identification and cloning of genes differentially expressed in the virulent strain of Mycobacterium tuberculosis. Gene 131:113–117. https://doi.org/10.1016/0378-1119(93)90678-v
Li HM, Qian X, Wang QG (2013) Heavy metals in atmospheric particulate matter: a comprehensive understanding is needed for monitoring and risk mitigation. Environ Sci Technol 47:13210–13211. https://doi.org/10.1021/es404751a
Lin H-H, Suk C-W, Lo H-L, Huang R-Y, Enarson R-Y, Chiang C-Y (2014) Indoor air pollution from solid fuel and tuberculosis: a systematic review and meta-analysis. Int J Tuberc Lung Dis 18:613–621. https://doi.org/10.5588/ijtld.13.0765
Loxham M, Cooper MJ, Gerlofs-Nijland ME et al (2013) Physicochemical characterization of airborne particulate matter at a mainline underground railway station. Environ Sci Technol 47:3614–3622. https://doi.org/10.1021/es304481m
Moodley Y (2008) The interaction of HIV and tuberculosis.Sci Res Essays 3:565–66. http://www.academicjournals.org/SRE
Nhung NTT, Amini H, Schindler C et al (2017) Short-term association between ambient air pollution and pneumonia in children: a systematic review and meta-analysis of time-series and case-crossover studies. Environ Pollut 230:1000–1008. https://doi.org/10.1016/j.envpol.2017.07.063
Peng Z, Liu C, Xu B, Kan H (2016) Long term exposure of ambient air pollution and mortality in a Chinese tuberculosis cohort. Sci Total Environ 580https://doi.org/10.1016/j.scitotenv.2016.12.128
Perrino C, Canepari S, Catrambone M (2013) Comparing the performance of Teflon and quartz membrane filters collecting atmospheric PM: influence of atmospheric water. Aerosol Air Qual Res 13:137–147. https://doi.org/10.4209/aaqr.2012.07.0167
Power AL, Tennant RK, Jones RT et al (2018) Monitoring impacts of urbanisation and industrialisation on air quality in the Anthropocene using urban pond sediments. Front Earth Sci 6:131. https://doi.org/10.3389/feart.2018.00131
Rajaei E, Hadadi M, Madadi M et al (2018) Outdoor air pollution affects tuberculosis development based on geographical information system modeling. Biomed Biotechnol Res J 2:39–45. https://doi.org/10.4103/bbrj.bbrj_5_18
Rivas-Santiago CE, Sarkar S, Osornio-Vargas Á et al (2015) Air pollution particulate matter alters antimycobacterial respiratory epithelium innate immunity. Infect Immun 83:2507–2517. https://doi.org/10.1128/IAI.03018-14
Roper C, Chubb LG, Cambal L, Tunno B, Clougherty JE, Mischler SE (2015) Characterization of ambient and extracted PM2.5 collected on filters for toxicology applications. Inhal Toxicol 27:673–681. https://doi.org/10.3109/08958378.2015.1092185
Sah D, Verma PK, Kumari KM, Lakhani A (2017) Chemical partitioning of fine particle-bound As, Cd, Cr, Ni Co, Pb and assessment of associated cancer risk due to inhalation, ingestion and dermal exposure. InhalToxicol 29:483–493. https://doi.org/10.1080/08958378.2017.1406563
Sarkar S, Rivas-Santiago CE, Ibironke OA et al (2019) Season and size of urban particulate matter differentially affect cytotoxicity and human immune responses to Mycobacterium tuberculosis. PloS one 14(7):e0219122. https://doi.org/10.1371/journal.pone.0219122
Sarkar S, Song Y, Sarkar S et al (2012) Suppression of the NF-ΚB pathway by diesel exhaust particles impairs human antimycobacterial immunity. J Immunol 188(6):2778–2793. https://doi.org/10.4049/jimmunol.1101380
Sharma R, Saikia UN, Sharma S, Verma I (2017) Activity of human beta defensin-1 and its motif against active and dormant Mycobacterium tuberculosis. Appl Microbiol Biotechnol 101:7239–48. https://doi.org/10.1007/s00253-017-8466-3
Sherman DR, Voskuil M, Schnappinger D, Liao R, Harrell MI, Schoolnik GK (2001) Regulation of the Mycobacterium tuberculosis hypoxic response gene encoding α-crystallin. PNAS 98:7534–7539. https://doi.org/10.1073/pnas.121172498
Sirakova TD, Dubey VS, Deb C et al (2006) Identification of a diacylglycerol acyltransferase gene involved in accumulation of triacylglycerol in Mycobacterium tuberculosis under stress. Microbiology 152:2717–2725. https://doi.org/10.1099/mic.0.28993-0
Smith GS, Schoenbach VJ, Richardson DB, Gammon MD (2014) North Carolina: an ecological study. Int J Environ Health Res 24(2):103–112. https://doi.org/10.1080/09603123.2013.800959
Torres M, Carranza C, Sarkar S et al (2019) Urban airborne particle exposure impairs human lung and blood Mycobacterium tuberculosis immunity. Thorax 74:675–683. https://doi.org/10.1136/thoraxjnl-2018-212529
Tufariello JM, Mi k, Xu J, et al (2006) Deletion of the Mycobacterium tuberculosis resuscitation-promoting factor Rv1009 gene results in delayed reactivation from chronic tuberculosis. Infect Immun 74:2985–2995. https://doi.org/10.1128/IAI.74.5.2985-2995.2006
Wang F, Chen T, Chang Q et al (2021) Respiratory diseases are positively associated with PM 2.5 concentrations in different areas of Taiwan. PLoS One 16(4):e0249694. https://doi.org/10.1371/journal.pone.0249694
Weinhold B (2006 ) Epigenetics: the science of change. Environ Health Perspect114(3). https://doi.org/10.1289/ehp.114-a160
Wong NS, Leung CC, Li Y et al (2017) PM2·5 concentration and elderly tuberculosis: analysis of spatial and temporal associations. The Lancet 390:S68. https://doi.org/10.1016/S0140-6739(17)33206-3
Xing YF, Xu YH, Shi MH, Lian YX (2016) The impact of PM2.5 on the human respiratory system. J Thorac Dis 8:E69-74. https://doi.org/10.3978/j.issn.2072-1439.2016.01.19
Yang A, Jedynska A, Hellack B et al (2014) Measurement of the oxidative potential of PM2.5 and its constituents: the effect of extraction solvent and filter type. Atmos Environ 83:35–42. https://doi.org/10.1016/j.atmosenv.2013.10.049
Yang J, Zhang M, Chen Y et al (2020a) A study on the relationship between air pollution and pulmonary tuberculosis based on the general additive model in Wulumuqi. China Int J Infect Dis 96:42–47. https://doi.org/10.1016/j.ijid.2020.03.032
Yang L, Li C, Tang X (2020) The impact of PM2.5 on the host defense of respiratory system. Front Cell Dev Biol 8:91. https://doi.org/10.3389/fcell.2020.00091
You S, Tong YW, Neoh KG, Dai Y, Wang CH (2016) On the association between outdoor PM2.5 concentration and the seasonality of tuberculosis for Beijing and Hong Kong. Environ Pollut 218:1170–1179. https://doi.org/10.1016/j.envpol.2016.08.071
Zhai YB, Liu XT, Chen HM et al (2014) Source identification and potential ecological risk assessment of heavy metals in PM2.5 from Changsha. Sci Total Environ 493:109–115. https://doi.org/10.1016/j.scitotenv.2014.05.106
Zhou Z, Liu Y, Duan F et al (2015) Transcriptomic analyses of the biological effects of airborne PM2.5 exposure on human bronchial epithelial cells. PLoS One 10:e0138267. https://doi.org/10.1371/journal.pone.0138267
Partial funding from Special Research Grant, PGIMER, Chandigarh.
Ethics approval and consent to participate
The study was approved by Institute Ethics Committee, PGIMER, Chandigarh with reference no: NK/4978/MD/442 dated 11.02.2019, and subjects were recruited after taking written informed consent.
Consent for publication
The authors declare no competing interests.
Communicated by: Ludek Blaha.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Below is the link to the electronic supplementary material.
About this article
Cite this article
Punniyamurthy, A., Sharma, S., Kaur, K. et al. PM2.5 mediated alterations in the in vitro human granuloma and its effect on reactivation of mycobacteria. Environ Sci Pollut Res 29, 14497–14508 (2022). https://doi.org/10.1007/s11356-021-16799-7