1887

Abstract

. (), the causative agent of tuberculosis, can survive as an intracellular parasite after entering macrophages via phagocytosis. strains are genotypically distinct and engage in diverse pathogen–host interactions, with different host immune responses triggered by different strains. Importantly, differences in intracellular accumulation and triggering of host macrophage responses during early infection stages are key determinants that shape the final outcomes of host innate immune responses to different strains.

. Clinical strains with different genotypes elicit different host innate immune responses .

. This work aimed to compare host innate immune responses elicited by genotypically diverse, clinically derived strains .

. RAW264.7 cells were infected with three lineage 2 and lineage 4 clinically derived strains and strain H37Rv. Strains were evaluated for differences in intracellular growth, induction of macrophage apoptosis, and induction of expression of proinflammatory cytokines and associated pattern recognition receptors.

. Highly variable cytokine profiles were observed subsequent to RAW264.7 cell infection with the different strains. The Beijing genotype strain, a modern Beijing strain belonging to lineage 2, induced milder host proinflammatory responses and less apoptosis and exhibited greater intracellular growth as compared to the other strains. Moreover, mRNA expression levels of in Beijing and MANU2 genotype strains exceeded corresponding levels obtained for the T1 genotype strain. Meanwhile, mRNA expression levels of toll-like receptor (TLR)-encoding genes and in macrophages infected with the Beijing genotype strain were higher than corresponding levels observed in MANU2 genotype strain-infected macrophages.

. The higher intracellular survival rate and lower level of host cell apoptosis associated with macrophage infection with the Beijing genotype strain indicated greater virulence of this strain relative to that of the other strains. Furthermore, immune responses induced by the Beijing genotype strain were unique in that this strain induced a weaker inflammatory response than was induced by T1 or MANU2 genotype strains. Nevertheless, additional evidence is needed to confirm that Beijing genotype strains possess greater virulence than strains with other genotypes.

Funding
This study was supported by the:
  • Scientific Research Project of Beijing Educational Committee (Award KM202010025001)
  • the Research Capability Promotion Project of Beijing TB and Thoracic Tumor Research Institute (Award KJ2021CX010)
    • Principle Award Recipient: YiLiu
  • the Capital Medical Development Special Foundation (Award 2020-2-1042)
    • Principle Award Recipient: ChuanYouLi
  • Beijing Key Clinical Speciality Project (Award 20201214)
    • Principle Award Recipient: ShenjieTang
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2022-11-28
2024-11-12
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References

  1. Coscolla M. Biological and Epidemiological Consequences of MTBC Diversity. Adv Exp Med Biol 2017; 1019:95–116 [View Article]
    [Google Scholar]
  2. Coscolla M, Gagneux S. Consequences of genomic diversity in Mycobacterium tuberculosis. Semin Immunol 2014; 26:431–444 [View Article]
    [Google Scholar]
  3. Etna MP, Giacomini E, Severa M, Coccia EM. Pro- and anti-inflammatory cytokines in tuberculosis: a two-edged sword in TB pathogenesis. Semin Immunol 2014; 26:543–551 [View Article]
    [Google Scholar]
  4. Sinsimer D, Huet G, Manca C, Tsenova L, Koo M-S et al. The phenolic glycolipid of Mycobacterium tuberculosis differentially modulates the early host cytokine response but does not in itself confer hypervirulence. Infect Immun 2008; 76:3027–3036 [View Article]
    [Google Scholar]
  5. Tanveer M, Hasan Z, Kanji A, Hussain R, Hasan R. Reduced TNF-alpha and IFN-gamma responses to central asian strain 1 and Beijing isolates of Mycobacterium tuberculosis in comparison with H37Rv strain. Trans R Soc Trop Med Hyg 2009; 103:581–587 [View Article]
    [Google Scholar]
  6. Marquina-Castillo B, García-García L, Ponce-de-León A, Jimenez-Corona M-E, Bobadilla-Del Valle M et al. Virulence, immunopathology and transmissibility of selected strains of Mycobacterium tuberculosis in a murine model. Immunology 2009; 128:123–133 [View Article]
    [Google Scholar]
  7. López B, Aguilar D, Orozco H, Burger M, Espitia C et al. A marked difference in pathogenesis and immune response induced by different Mycobacterium tuberculosis genotypes. Clin Exp Immunol 2003; 133:30–37 [View Article]
    [Google Scholar]
  8. Reiling N, Homolka S, Walter K, Brandenburg J, Niwinski L et al. Clade-specific virulence patterns of Mycobacterium tuberculosis complex strains in human primary macrophages and aerogenically infected mice. mBio 2013; 4:e00250-13 [View Article]
    [Google Scholar]
  9. Brudey K, Driscoll JR, Rigouts L, Prodinger WM, Gori A et al. Mycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology. BMC Microbiol 2006; 6:23 [View Article]
    [Google Scholar]
  10. López-Agudelo VA, Baena A, Barrera V, Cabarcas F, Alzate JF et al. Dual RNA sequencing of Mycobacterium tuberculosis-infected human splenic macrophages reveals a strain-dependent host-pathogen response to infection. Int J Mol Sci 2022; 23:1803 [View Article]
    [Google Scholar]
  11. Liu Q, Wang D, Martinez L, Lu P, Zhu L et al. Mycobacterium tuberculosis Beijing genotype strains and unfavourable treatment outcomes: a systematic review and meta-analysis. Clin Microbiol Infect 2020; 26:180–188 [View Article]
    [Google Scholar]
  12. Liu Y, Zhang XX, Yu JJ, Liang C, Xing Q et al. Tuberculosis relapse is more common than reinfection in Beijing, China. Infect Dis 2020; 52:858–865 [View Article]
    [Google Scholar]
  13. Li D, Song Y, Yang P, Li X, Zhang A-M et al. Genetic diversity and drug resistance of Mycobacterium tuberculosis in Yunnan, China. J Clin Lab Anal 2019; 33:e22884 [View Article]
    [Google Scholar]
  14. Zheng C, Li S, Luo Z, Pi R, Sun H et al. Mixed infections and rifampin heteroresistance among Mycobacterium tuberculosis clinical isolates. J Clin Microbiol 2015; 53:2138–2147 [View Article]
    [Google Scholar]
  15. Xing L, Liu R, Li Q, Peng Z, Zhu C. Clinical and genotypic characteristics of childhood tuberculosis in Chongqing, China. Eur J Clin Microbiol Infect Dis 2012; 31:1735–1739 [View Article]
    [Google Scholar]
  16. Zhao Y, Feng Q, Tang K, Zhang C, Sun H et al. The population structure of drug-resistant Mycobacterium tuberculosis clinical isolates from Sichuan in China. Infect Genet Evol 2012; 12:718–724 [View Article]
    [Google Scholar]
  17. Rastogi S, Briken V. Interaction of Mycobacteria with host cell inflammasomes. Front Immunol 2022; 13:791136 [View Article]
    [Google Scholar]
  18. Portevin D, Gagneux S, Comas I, Young D. Human macrophage responses to clinical isolates from the Mycobacterium tuberculosis complex discriminate between ancient and modern lineages. PLoS Pathog 2011; 7:e1001307 [View Article]
    [Google Scholar]
  19. Manca C, Reed MB, Freeman S, Mathema B, Kreiswirth B et al. Differential monocyte activation underlies strain-specific Mycobacterium tuberculosis pathogenesis. Infect Immun 2004; 72:5511–5514 [View Article]
    [Google Scholar]
  20. Mayer-Barber KD, Andrade BB, Barber DL, Hieny S, Feng CG et al. Innate and adaptive interferons suppress IL-1α and IL-1β production by distinct pulmonary myeloid subsets during Mycobacterium tuberculosis infection. Immunity 2011; 35:1023–1034 [View Article]
    [Google Scholar]
  21. Martinez AN, Mehra S, Kaushal D. Role of interleukin 6 in innate immunity to Mycobacterium tuberculosis infection. J Infect Dis 2013; 207:1253–1261 [View Article]
    [Google Scholar]
  22. Mourik BC, de Steenwinkel JEM, de Knegt GJ, Huizinga R, Verbon A et al. Mycobacterium tuberculosis clinical isolates of the Beijing and East-African Indian lineage induce fundamentally different host responses in mice compared to H37Rv. Sci Rep 2019; 9:19922 [View Article]
    [Google Scholar]
  23. Chakraborty P, Kulkarni S, Rajan R, Sainis K. Drug resistant clinical isolates of Mycobacterium tuberculosis from different genotypes exhibit differential host responses in THP-1 cells. PLoS One 2013; 8:e62966 [View Article]
    [Google Scholar]
  24. María Irene C-C, Juan Germán R-C, Gamaliel L-L, Dulce Adriana M-E, Estela Isabel B et al. Profiling the immune response to Mycobacterium tuberculosis Beijing family infection: a perspective from the transcriptome. Virulence 2021; 12:1689–1704 [View Article] [PubMed]
    [Google Scholar]
  25. Tong J, Meng L, Bei C, Liu Q, Wang M et al. Modern Beijing sublineage of Mycobacterium tuberculosis shift macrophage into a hyperinflammatory status. Emerg Microbes Infect 2022; 11:715–724 [View Article] [PubMed]
    [Google Scholar]
  26. Wong EA, Evans S, Kraus CR, Engelman KD, Maiello P et al. IL-10 Impairs local immune response in lung granulomas and lymph nodes during early Mycobacterium tuberculosis infection. J Immunol 2020; 204:644–659 [View Article]
    [Google Scholar]
  27. Higgins DM, Sanchez-Campillo J, Rosas-Taraco AG, Lee EJ, Orme IM et al. Lack of IL-10 alters inflammatory and immune responses during pulmonary Mycobacterium tuberculosis infection. Tuberculosis (Edinb) 2009; 89:149–157 [View Article] [PubMed]
    [Google Scholar]
  28. Eum S-Y, Lee Y-J, Min J-H, Kwak H-K, Hong M-S et al. Association of antigen-stimulated release of tumor necrosis factor-alpha in whole blood with response to chemotherapy in patients with pulmonary multidrug-resistant tuberculosis. Respiration 2010; 80:275–284 [View Article] [PubMed]
    [Google Scholar]
  29. Sai Priya VH, Anuradha B, Latha Gaddam S, Hasnain SE, Murthy KJR et al. In vitro levels of interleukin 10 (IL-10) and IL-12 in response to a recombinant 32-kilodalton antigen of Mycobacterium bovis BCG after treatment for tuberculosis. Clin Vaccine Immunol 2009; 16:111–115 [View Article] [PubMed]
    [Google Scholar]
  30. Parwati I, van Crevel R, van Soolingen D. Possible underlying mechanisms for successful emergence of the Mycobacterium tuberculosis Beijing genotype strains. Lancet Infect Dis 2010; 10:103–111 [View Article] [PubMed]
    [Google Scholar]
  31. Parwati I, Alisjahbana B, Apriani L, Soetikno RD, Ottenhoff TH et al. Mycobacterium tuberculosis Beijing genotype is an independent risk factor for tuberculosis treatment failure in Indonesia. J Infect Dis 2010; 201:553–557 [View Article] [PubMed]
    [Google Scholar]
  32. Hanekom M, Gey van Pittius NC, McEvoy C, Victor TC, Van Helden PD et al. Mycobacterium tuberculosis Beijing genotype: a template for success. Tuberculosis (Edinb) 2011; 91:510–523 [View Article] [PubMed]
    [Google Scholar]
  33. Krakauer T. Inflammasomes, autophagy, and cell death: the trinity of innate host defense against intracellular bacteria. Mediators Inflamm 2019; 2019:2471215 [View Article]
    [Google Scholar]
  34. Mishra A, Akhtar S, Jagannath C, Khan A. Pattern recognition receptors and coordinated cellular pathways involved in tuberculosis immunopathogenesis:emerging concepts and perspectives. Mol Immunol 2017; 87:240–248 [View Article]
    [Google Scholar]
  35. Yu X, Zeng J, Xie J. Navigating through the maze of TLR2 mediated signaling network for better mycobacterium infection control. Biochimie 2014; 102:1–8 [View Article] [PubMed]
    [Google Scholar]
  36. Wang T, Lafuse WP, Zwilling BS. Regulation of toll-like receptor 2 expression by macrophages following Mycobacterium avium infection. J Immunol 2000; 165:6308–6313 [View Article] [PubMed]
    [Google Scholar]
  37. Bao M, Yi Z, Fu Y. Activation of TLR7 inhibition of Mycobacterium tuberculosis survival by autophagy in RAW 264.7 macrophages. J Cell Biochem 2017; 118:4222–4229 [View Article]
    [Google Scholar]
  38. Mishra BB, Moura-Alves P, Sonawane A, Hacohen N, Griffiths G et al. Mycobacterium tuberculosis protein ESAT-6 is a potent activator of the NLRP3/ASC inflammasome. Cell Microbiol 2010; 12:1046–1063 [View Article]
    [Google Scholar]
  39. Mishra BB, Rathinam VAK, Martens GW, Martinot AJ, Kornfeld H et al. Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3 inflammasome-dependent processing of IL-1β. Nat Immunol 2013; 14:52–60 [View Article] [PubMed]
    [Google Scholar]
  40. Hernandez-Cuellar E, Tsuchiya K, Hara H, Fang R, Sakai S et al. Cutting edge: nitric oxide inhibits the NLRP3 inflammasome. J Immunol 2012; 189:5113–5117 [View Article] [PubMed]
    [Google Scholar]
  41. Wei M, Wang L, Wu T, Xi J, Han Y et al. NLRP3 Activation was regulated by DNA methylation modification during Mycobacterium tuberculosis infection. Biomed Res Int 2016; 2016:4323281 [View Article]
    [Google Scholar]
  42. van Embden JD, van Gorkom T, Kremer K, Jansen R, van Der Zeijst BA et al. Genetic variation and evolutionary origin of the direct repeat locus of Mycobacterium tuberculosis complex bacteria. J Bacteriol 2000; 182:2393–2401 [View Article] [PubMed]
    [Google Scholar]
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