Innate immune receptors in development of Mycobacterium tuberculosis infection

Cover Page

Cite item


According to the World Health Organization, over 10 million new tuberculosis cases are reported annually worldwide. According to the 2017 Federal State Statistics Service Report, incidence rate for active TB infection in the Russian Federation was 109.8 cases per 100,000 population, of which 41.3% accounted for chronic disease form. Regardless of climatic conditions, high prevalence of TB infection, is not only due to high Mycobacterium tuberculosis viability, but also its ability for long persistence in human body and reactivation after an unlimited period of dormancy. The outcome of infection is largely determined by host immunoreactivity and its ability to develop protective immune response. In addition, status of immune system also underlies tuberculosis course after the onset: either as a localized form, or as a form with extensive damage to the lungs and even other organs observed in generalized infection. In recent decades, a great attention was paid to examining mechanisms of adaptive cell immunity played in pathogenesis of TB infection. No doubt, adaptive immunity is a powerful defense system providing a targeted specific immune response, but now it is becoming clear that it represents solely an effector arm of innate immunity. Innate immunity is a phylogenetically more ancient, inherited system largely aimed at ensuring rapid pathogen elimination and preventing development of infection at early stages when adaptive immunity ongoing antigen-specific maturation. Mechanisms of innate immunity mediated by cells, diverse receptors, molecules and their complexes, found on various cells. Activation of innate immunity begins with recognition of conserved molecular groups present in various pathogens called pathogen-associated molecular patterns (PAMPs), which are sensed by pathogen recognition receptors (PRRs). Here, we review current data on the role of innate receptors in recognizing M. tuberculosis-derived PAMPs, production of immunoregulatory cytokines and activation of signaling pathways playing a crucial role in the regulation of necroptosis, apoptosis and autophagy of infected macrophages. Significance of innate mucosal factors in implementing immune response to M. tuberculosis is discussed. In particular, Toll-like receptors, scavenger-receptors, mannose receptor, DC-SIGN etc. were described to participate in development of M. tuberculosis immunity. The data on single nucleotide polymorphic variants for innate genes are shown, which predispose to developing tuberculosis and affecting its course.

About the authors

A. V. Lapshtaeva

National Research Ogarev Mordovia State University, Medical Institute

Author for correspondence.

Associate Professor, Department of Immunology, Microbiology and Virology.

430005, Saransk, Bol’shevistskaya str., 68, Phone: +7 (927) 177-35-55

Russian Federation

E. A. Zhivechkova

Pirogov Russian National Research Medical University (RNRMU)


Resident of the Department of Hospital Therapy No. 2, Faculty of Medicine.


Russian Federation

I. V. Sychev

National Research Ogarev Mordovia State University, Medical Institute


PhD Student.

Saransk Russian Federation

I. V. Evsegneeva

I.M. Sechenov First Moscow State Medical University


PhD, MD (Medicine), Professor, Professor of the Department of Clinical Immunology and Allergology.

Moscow Russian Federation

V. V. Novikov

N.I. Lobachevskii National Research Nizhny Novgorod State University; I.N. Blokhina Nizhny Novgorod Research Institute of Epidemiology and Microbiology


PhD, MD (Medicine), Professor, Head of the Department of Molecular Biology and Immunology, N.I. Lobachevskii NRNNSU; Head of the Department of Immunochemisrty, I.N. Blokhina Nizhny Novgorod RIEM.

Nizhny Novgorod


  1. Герасимов А.Н., Михеева И.В. Эпидемиологическая ситуация с туберкулезом в России — кажущееся благополучие и скрытые угрозы // Тихоокеанский медицинский журнал. 2018. № 3. С. 75—78.
  2. Звонкова С.Г., Зоркальцева Е.Ю., Огарков О.Б. Изучение особенностей полиморфизма генов DC-SIGN-336A/G, MCP1-2518A/G, INFy +874A/T и конституциональных типов у детей с туберкулезной инфекцией // Acta Biomedica Scientifica. 2011. Т. 78, № 2. С. 198-200.
  3. Малышев И.Ю., Лямина С.В., Шимшелашвили Ш.Л., Вассерман Е.Н. Функциональные ответы альвеолярных макрофагов, сурфактантный белок D и заболевания легких // Пульмонология. 2014. № 3. С. 101-107.
  4. Синьков В.В., Огарков О.Б., Зоркальцева Е.Ю., Скворцова Р.Г., Савилов Е.Д., Воробьева Д.В., Корчина С.И., Жданов С.Н., Косенкова Д.В., Медведева Т.В. Полиморфизм генов DC-SIGN —336A/G, MCP1 —2518A/G, IFNy +874A/T у больных легочным туберкулезом в Иркутской области // Сибирский медицинский журнал. 2009. Т. 90, № 7. С. 30—33.
  5. Astarie-Dequeker C., Le Guyader L., Malaga W., Seaphanh F.-K., Chalut C., Lopez A., Guilhot C. Phthiocerol dimycocerosates of M. tuberculosis participate in macrophage invasion by inducing changes in the organization of plasma membrane lipids. PLoS Pathog., 2009, vol. 5, no. 2: e1000289. doi: 10.1371/journal.ppat.1000289
  6. Astarie-Dequeker C., N’Diaye E.N., Cabec V.Le, Rittig M.G., Prandi J., Maridonneau-Parini I. The mannose receptor mediates uptake of pathogenic and nonpathogenic mycobacteria and bypasses bactericidal responses in human macrophages. Infect. Immun., 1999, vol. 67, no. 2, pp. 469—477.
  7. Azad A.K., Sadee W., Schlesinger L.S. Innate immune gene polymorphisms in tuberculosis. Infect. Immun., 2012, vol. 80, no. 10, pp. 3343-3359. doi: 10.1128/IAI.00443-12
  8. Azad A.K., Torrelles J.B., Schlesinger L.S. Mutation in the DC-SIGN cytoplasmic triacidic cluster motif markedly attenuates receptor activity for phagocytosis and endocytosis of mannose-containing ligands by human myeloid cells. J. Leukoc. Biol., 2008, vol. 84, no. 6, pp. 1594-1603. doi: 10.1189/jlb.0308192
  9. Bandyopadhyay U., Chadha A., Gupta P., Tiwari B., Bhattacharyya K., Popli S., Raman R., Brahamachari V., Singh Y., Malhotra P., Natarajan K. Suppression of Toll-like receptor 2—mediated proinflammatory responses by Mycobacterium tuberculosis protein Rv3529c. J. Leukoc. Biol., 2017, vol. 102, no. 5,pp. 1249-1259. doi: 10.1189/jlb.4A0217-042R
  10. 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, vol. 118, no. 12, pp. 4222-4229. doi: 10.1002/jcb.26072
  11. Barreiro L.B., Neyrolles O., Babb C.L., Tailleux L., Quach H., McElreavey K., Helden P.D. Van, Hoal E.G., Gicquel B., Quintana-Murci L. Promoter variation in the DC-SIGN-encoding gene CD209 is associated with tuberculosis. PLoSMed., 2006, vol. 3, no. 2: e20. doi: 10.1371/journal.pmed.0030020
  12. Beharka A.A., Gaynor C.D., Kang B.K., Voelker D.R., McCormack F.X., Schlesinger L.S. Pulmonary surfactant protein A up-regulates activity of the mannose receptor, a pattern recognition receptor expressed on human macrophages. J. immunol., 2002, vol. 169, no. 7,pp. 3565-3573. doi: 10.4049/jimmunol.169.7.3565
  13. Ben-Ali M., Barbouche M.-R., Bousnina S., Chabbou A., Dellagi K. Toll-like receptor 2 Arg677Trp polymorphism is associated with susceptibility to tuberculosis in Tunisian patients. Clin. Diagnost. Lab. Immunol., 2004, vol. 11, no. 3, pp. 625-626. doi: 10.1128/CDLI.11.3.625-626.2004
  14. Bharti D., Kumar A., Mahla R.S., Kumar S., Ingle H., Shankar H., Joshi B., Raut A.A., Kumar H. The role ofTLR9 polymorphism in susceptibility to pulmonary tuberculosis. Immunogenetics, 2014, vol. 66, no. 12,pp. 675-681. doi: 10.1007/s00251-014-0806-1
  15. Boily-Larouche G., Zijenah L.S., Mbizvo M., Ward B.J., Roger M. DC-SIGN and DC-SIGNR genetic diversity among different ethnic populations: Potential implications for pathogen recognition and disease susceptibility. Hum. Immunol., 2007, vol. 68, no. 6, pp. 523-530. doi: 10.1016/j.humimm.2007.02.002
  16. Bowdish D.M.E., Sakamoto K., Kim M., Kroos M., Mukhopadhyay S., Leifer C.A., Tryggvason K., Gordon S., Russell D.G. MARCO, TLR2, and CD 14 are required for macrophage cytokine responses to mycobacterial trehalose dimycolate and Mycobacterium tuberculosis. PLoS Pathog., 2009, vol. 5, no. 6: e1000474. doi: 10.1371/journal.ppat.1000474
  17. Brooks M.N., Rajaram M.V.S., Azad A.K., Amer A.O., Valdivia-arenas M.A., Park J., Nunez G., Schlesinger L.S. NOD2 controls the nature of the inflammatory response and subsequent fate of Mycobacterium tuberculosis and M. bovis BCG in human macrophages. Cell. Microbiol, 2010, vol. 13, no. 3,pp. 402-418. doi: 10.1111/j.1462-5822.2010.01544.x
  18. Capparelli R., Iannaccone M., Palumbo D., Medaglia C., Moscariello E., Russo A., Iannelli D. Role played by human mannosebinding lectin polymorphisms in pulmonary tuberculosis. J. Infect. Dis., 2009, vol. 199, no. 5, pp. 666- 672. doi: 10.1086/596658
  19. Ceylan E., Karkucak M., Coban H., Karadag M., Yakut T. Evaluation of TNF-alpha gene (G308A) and MBL2 gene codon 54 polymorphisms in Turkish patients with tuberculosis. J. Infect. Public Health, 2017, vol. 10, no. 6, pp. 774-777. doi: 10.1016/j.jiph.2016.11.003
  20. Chieppa M., Bianchi G., Doni A., Prete A., Del, Sironi M., Laskarin G., Monti P., Piemonti L., Biondi A., Mantovani A., Introna M., Allavena P. Cross-linking of the mannose receptor on monocyte-derived dendriticcells activates an anti-inflammatory immunosuppressive program. J. Immunol., 2003, vol. 171, no. 9, pp. 4552-4560. doi: 10.4049/jimmunol.171.9.4552
  21. Chroneos Z.C., Midde K., Sever-Chroneos Z., Jagannath C. Pulmonary surfactant and tuberculosis. Tuberculosis, 2009, vol. 89, suppl. 1, pp. S10-14. doi: 10.1016/S1472-9792(09)70005-8
  22. Chua J., Vergne I., Master S., Deretic V. A tale of two lipids: Mycobacterium tuberculosis phagosome maturation arrest. Curr. Opin. Microbiol., 2004, vol. 7, no. 1, pp. 71-77. doi: 10.1016/j.mib.2003.12.011
  23. Coulombe F., Divangahi M., Veyrier F., Leseleuc L. De, Gleason J.L., Yang Y., Kelliher M.A., Pandey A.K., Sassetti C.M., Reed M.B., Behr M.A. Increased NOD2-mediated recognition of N-glycolyl muramyl dipeptide. J. Exp. Med., 2009, vol. 206, no. 8, pp. 1-8. doi: 10.1084/jem.20081779
  24. Court N., Vasseur V., Vacher R., Fremond C., Shebzukhov Y., Yeremeev V.V., Maillet I., Nedospasov S.A., Gordon S., Fallon P.G., Suzuki H., Ryffel B., Quesniaux V.F.J. Partial redundancy of the pattern recognition receptors, scavenger receptors, and C-type lectins for the long-term control of Mycobacterium tuberculosis infection. J. Immunol., 2010, vol. 184, no. 12, pp. 7057-7070. doi: 10.4049/jimmunol.1000164
  25. Dalgic N., Tekin D., Kayaalti Z., Soylemezoglu T., Cakir E., Kilic B., Kutlubay B., Sancar M., Odabasi M. Arg753Gln polymorphism of the human Toll-like receptor 2 gene from infection to disease in pediatric tuberculosis. Hum. Immunol., 2011, vol. 72, no. 5, pp. 440-445. doi: 10.1016/j.hummim.2011.02.001
  26. De Oliveira L.R., Peresi E., Golim Mde A., Gatto M., Araujo Junior J.P., da Costa E.A., Ayres J.A., Fortes M.R., Calvi S.A. Analysis of Toll-like receptors, iNOS and cytokine profiles in patients with pulmonary tuberculosis during anti-tuberculosis treatment. PLoS One, 2014, vol. 9, no. 2: e88572. doi: 10.1371/journal.pone.0088572
  27. DeFife K.M., Jenney C.R., McNally A.K., Colton E., Anderson J.M. Interleukin-13 induces human monocyte/macrophage fusion and macrophage mannose receptor expression. J. Immunol., 1997, vol. 158, no. 7, pp. 3385-3390.
  28. Dodd C.E., Pyle C.J., Glowinski R., Rajaram M.V.S., Schlesinger L.S. CD36-mediated uptake of surfactant lipids by human macrophages promotes intracellular growth of Mycobacterium tuberculosis. J. Immunol., 2016, vol. 197, no. 12, pp. 4727-4735. doi: 10.4049/jimmunol.1600856
  29. Enomoto Y., Hagiwara E., Komatsu S., Nishihira R., Baba T., Ogura T. Comparison of biomarkers of pulmonary tuberculosis activity — serum surfactant proteins A and D, KL-6, C-reactive protein, and erythrocyte sedimentation rate. Kekkaku: [Tuberculosis]., 2014, vol. 89, no. 7, pp. 637—642.
  30. Ferguson J.S., Martin J.L., Azad A.K., McCarthy T.R., Kang P.B., Voelker D.R., Crouch E.C., Schlesinger L.S. Surfactant protein D increases fusion of Mycobacterium tuberculosis-containing phagosomes with lysosomes in human macrophages. Infect. Immun., 2006, vol. 74, no. 12,pp. 7005- 7009. doi: 10.1128/IAI.01402-06
  31. Figdor C.G., Kooyk van Y., Adema G.J. C-type lectin receptors on dendritic cells and langerhans cells. Nat. Rev. Immunol., 2002, vol. 2, no. 2, pp. 77-84. doi: 10.1038/nri723
  32. Floras J., Lin H., Garcia A., Salazar M.A., Guo X., DiAngelo S., Montano M., Luo J., Pardo A., Selman M. Surfactant protein genetic marker alleles identify a subgroup of tuberculosis in a Mexican population. J. Infect. Dis., 2000, vol. 182, no. 5, pp. 1473—1478. doi: 10.1086/315866
  33. Fratti R.A., Chua J., Vergne I., Deretic V. Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest. Proc. Nati. Acad. Sci. USA, 2003, vol. 100, no. 9, pp. 5437—5442. doi: 10.1073/pnas.0737613100
  34. Fremond C.M., Yeremeev V., Nicolle D.M., Jacobs M., Quesniaux V.F., Ryffel B. Fatal Mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88. J. Clin. Invest., 2004, vol. 114, no. 12, pp. 1790—1799. doi: 10.1172/JCI21027
  35. Garred P., Richter C., Andersen A.B., Madsen H.O., Mtoni I., Svejgaard A., Shao J. Mannan-binding lectin in the sub-Saharan HIV and tuberculosis epidemics. Scand. J. Immunol., 1997, vol. 46, no. 2, pp. 204—208.
  36. Geijtenbeek T.B.H., Vliet S.J. van, Koppel E.A., Sanchez-Hernandez M., Vandenbroucke-Grauls C.M.J.E., Appelmelk B., Kooyk van Y. Mycobacteria Target DC-SIGN to Suppress Dendritic Cell Function. J. Exp. Med., 2003, vol. 197, no. 1, pp. 7—17. doi: 10.1084/jem.20021229
  37. Geissmann F., Manz M.G., Jung S., Sieweke M.H., Merad M., Ley K. Development of monocytes, macrophages, and dendritic cells. Science, 2010, vol. 327, no. 5966,pp. 656— 661. doi: 10.1126/science.1178331
  38. Gomez L.M., Anaya J.M., Sierra-Filardi E., Cadena J., Corbi A., Martin J. Analysis of DC-SIGN (CD209) Functional variants in patients with tuberculosis. Hum. Immunol., 2006, vol. 67, no. 10, pp. 808—811. doi: 10.1016/j.humimm.2006.07.003
  39. Gupta D., Sharma S., Singhal J., Satsangi A.T., Antony C., Natarajan K. Suppression of TLR2-induced IL-12, reactive oxygen species, and inducible nitric oxide synthase expression by Mycobacterium tuberculosis antigens expressed inside macrophages during the course of infection. J. Immunol, 2010, vol. 184, no. 10, pp. 5444—5455. doi: 10.4049/jimmunol.0903283
  40. Guzel A., Karadag A., Okuyucu A., Alacam H., Kucuk Y. The evaluation of serum surfactant protein D (SP-D) levels as a biomarker of lung injury in tuberculosis and different lung diseases. Clin. Lab., 2014, vol. 60, no. 7, pp. 1091—1098.
  41. Harding C.V., Boom W.H. Regulation of antigen presentation by Mycobacterium tuberculosis: a role for Toll-like receptors. Nat. Rev. Microbiol., 2010, vol. 8, no. 4, pp. 296—307. doi: 10.1038/nrmicro2321
  42. Harriff M.J., Cansler M.E., Toren K.G., Canfield E.T., Kwak S., Gold M.C., Lewinsohn D.M. Human lung epithelial cells contain Mycobacterium tuberculosis in a late endosomal vacuole and are efficiently recognized by CD8+ T cells. PLoS One, 2014, vol. 9, no. 5: e97515. doi: 10.1371/journal.pone.0097515
  43. Hartel C., Rupp J., Hoegemann A., Bohler A., Spiegler J., Otte S. Von, Roder K., Schultz C., Gopel W. 159C > T CD14 genotype — Functional effects on innate immune responses in term neonates. Hum. Immunol., 2008, pp. 338—343. doi: 10.1016/j.humimm.2008.04.011
  44. Hawkes M., Li X., Crockett M., Diassiti A., Finney C., Min-Oo G., Liles W.C., Liu J., Kain K.C. CD36 deficiency attenuates experimental mycobacterial infection. BMC Infect. Dis., 2010, vol. 10:299. doi: 10.1186/1471-2334-10-299
  45. Heldwein K.A., Fenton M.J. The role of Toll-like receptors in immunity against mycobacterial infection. Microbes Infect., 2002, vol. 4, no. 9, pp. 937-944. doi: 10.1016/S1286-4579(02)01611-8
  46. Henning L.N., Azad A.K., Parsa K.V.L., Crowther J.E., Tridandapani S., Schlesinger L.S. Pulmonary surfactant protein a regulates TLR expression and activity in human macrophages. J. Immunol., 2008, vol. 180, no. 2, pp. 7847-7858. doi: 10.4049/jim-munol.180.12.7847
  47. Hsieh M.H., Ou C.Y., Hsieh W.Y., Kao H.F., Lee S.W., Wang J., Wu L.S.H. Functional analysis of genetic variations in surfactant protein D in Mycobacterial infection and their association with tuberculosis. Front. Immunol., 2018, vol. 9. doi: 10.3389/fimmu.2018.01543
  48. Jo E.K. Mycobacterial interaction with innate receptors: TLRs, C-type lectins, and NLRs. Curr. Opin. Infect. Dis., 2008, vol. 21, no. 3,pp. 279-286. doi: 10.1097/QCO.0b013e3282f88b5d
  49. Jo E.K., Yang C.S., Choi C.H., Harding C .V. Intracellular signalling cascades regulating innate immune responses to Mycobacteria: bzzzranching out from Toll-like receptors. Cell. Microbiol., 2007, vol. 9, no. 5, pp. 1087-1098. doi: 10.1111/j.1462-5822.2007.00914.x
  50. Kang P.B., Azad A.K., Torrelles J.B., Kaufman T.M., Beharka A., Tibesar E., DesJardin L.E., Schlesinger L.S. The human macrophage mannose receptor directs Mycobacterium tuberculosis lipoarabinomannan-mediated phagosome biogenesis. J. Exp. Med, 2005, vol. 202, no. 7, pp. 987-999. doi: 10.1084/jem.20051239
  51. Kawai T., Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat. Immunol., 2010, vol. 11, no. 5, pp. 373-384. doi: 10.1038/ni.1863
  52. Khan A., Mann L., Papanna R., Lyu M.-A., Singh C.R., Olson S., Eissa N.T., Cirillo J., Das G., Hunter R.L., Jagannath C. Mesenchymal stem cells internalize Mycobacterium tuberculosis through scavenger receptors and restrict bacterial growth through autophagy. Sci. Rep., 2017, vol. 7, no. 1. doi: 10.1038/s41598-017-15290-z
  53. Khan N., Pahari S., Vidyarthi A., Aqdas M., Agrewala J.N. NOD-2 and TLR4 signaling reinforces the efficacy of dendritic cells and reduces the dose of TB drugs against Mycobacterium tuberculosis. J. Innate Immun., 2016, vol. 8, no. 3, pp. 228-242. doi: 10.1159/000439591
  54. Konowich J., Gopalakrishnan A., Dietzold J., Verma S., Bhatt K., Rafi W., Salgame P. Divergent functions of TLR2 on hematopoietic and nonhematopoietic cells during chronic Mycobacterium tuberculosis infection. J. Immunol., 2016, vol. 198, no. 2, pp. 741-748. doi: 10.4049/jimmunol.1601651
  55. Kusner D.J. Mechanisms of mycobacterial persistence in tuberculosis. Clin. Immunol., 2005, vol. 114, no. 3, pp. 239-247. doi: 10.1016/j.clim .2004.07.016
  56. Lee J.Y., Hwang E.H., Kim D.J., Oh S.M., Lee K.B., Shin S.J., Park J.H. The role of nucleotide-binding oligomerization domain 1 during cytokine production by macrophages in response to Mycobacterium tuberculosis infection. Immunobiology, 2016, vol. 221, no. 1,pp. 70-75. doi: 10.1016/j.imbio.2015.07.020
  57. Lee M.S., Kim Y.J. Signaling pathways downstream of pattern-recognition receptors and their cross talk. Annu. Rev. Biochem., 2007, vol. 76,pp. 447-480. doi: 10.1146/annurev.biochem.76.060605.122847
  58. Li Y., Wang Y., Liu X. The role of airway epithelial cells in response to mycobacteria infection. Clin. Dev. Immunol., 2012, vol. 2012. doi: 10.1155/2012/791392
  59. Liu P.T., Stenger S., Li H., Wenzel L., Tan B.H., Krutzik S.R., Ochoa M.T., Schauber J., Wu K., Meinken C., Kamen D.L., Wagner M., Bals R., Steinmeyer A., Zugel U., Gallo R.L, Eisenberg D., Hewison M., Hollis B.W., Adams J.S., Bloom B.R., Modlin R.L.Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science, 2006, vol. 311, no. 5768, pp. 1770-1773. doi: 10.1126/science.1123933
  60. Lugo-Villarino G., Hudrisier D., Tanne A., Neyrolles O. C-type lectins with a sweet spot for Mycobacterium tuberculosis. Eur. J. Microbiol. Immunol., 2011, vol. 1, no. 1, pp. 25-40. doi: 10.1556/EuJMI. 1.2011.1.6
  61. Lugo-Villarino G., Troegeler A., Balboa L., Lastrucci C., Duval C., Mercier I., Benard A., Capilla F., Saati T. Al, Poincloux R., Kondova I., Verreck F.A.W., Cougoule C., Maridonneau-Parini I., Sasiain M.D.C., Neyrolles O. The C-type lectin receptor DC-SIGN has an anti-inflammatory role in human M(IL-4) macrophages in response to Mycobacterium tuberculosis. Front. Immunol., 2018, vol. 9:1123. doi: 10.3389/fimmu.2018.01123
  62. Lv J., He X., Wang H., Wang Z., Kelly G.T., Wang X., Chen Y., Wang T., Qian Z. TLR4-NOX2 axis regulates the phagocytosis and killing of Mycobacterium tuberculosis by macrophages. BMCPulm. Med., 2017, vol. 17, no. 1,p. 194. doi: 10.1186/s12890-017-0517-0
  63. Maes E., Coddeville B., Kremer L., Guerardel Y. Polysaccharide structural variability in mycobacteria: Identification and characterization of phosphorylated mannan and arabinomannan. Glycoconj. J., 2007, vol. 24, no. 8, pp. 439- 448. doi: 10.1007/s10719-007-9036-1
  64. Malik S., Greenwood C.M.T., Eguale T., Kifle A., Beyene J., Habte A., Tadesse A., Gebrexabher H., Britton S., Schurr E. Variants of the SFTPA1 and SFTPA2 genes and susceptibility to tuberculosis in Ethiopia. Hum. Genet., 2006, vol. 118, no. 6, pp. 752-759. doi: 10.1007/s00439-005-0092-y
  65. Martinez-Pomares L., Reid D.M., Brown G.D., Taylor P.R., Stillion R.J., Linehan S.A., Zamze S., Gordon S., Wong S.Y.C. Analysis of mannose receptor regulation by IL-4, IL-10, and proteolytic processing using novel monoclonal antibodies. J. Leukocyte Biol, 2003, vol. 73, no. 5,pp. 604- 613. doi: 10.1189/jlb.0902450
  66. Matsushita M., Endo Y., Fujita T. Structural and functional overview of the lectin complement pathway: Its molecular basis and physiological implication. Arch. Immunol. Ther. Exp, 2013, vol. 61, no. 4,pp. 273-283. doi: 10.1007/s00005-013-0229-y
  67. McBride A., Konowich J., Salgame P. Host defense and recruitment of Foxp3+ T regulatory cells to the lungs in chronic mycobacterium tuberculosis infection requires Toll-like receptor 2. PLoS Pathog, 2013, vol. 9, no. 6: e1003397. doi: 10.1371/journal.ppat.1003397
  68. McGreal E.P., Miller J.L., Gordon S. Ligand recognition by antigen-presenting cell C-type lectin receptors. Curr. Opin. Immunol., 2005, vol. 17, no. 1,pp. 18-24. doi: 10.1016/j.coi.2004.12.001
  69. Mishra A.K., Driessen N.N., Appelmelk B.J., Besra G.S. Lipoarabinomannan and related glycoconjugates: structure, biogenesis and role in Mycobacterium tuberculosis physiology and host-pathogen interaction. FEMS Microbiol. Rev., 2011, vol. 35, no. 6, pp. 1126-1157
  70. Mittal M., Biswas S.K., Singh V., Arela N., Katoch V.M., Das R., Yadav V.S., Bajaj B., Mohanty K.K. Association of Toll like receptor 2 and 9 gene variants with pulmonary tuberculosis: exploration in a northern Indian population. Mol. Biol. Rep., 2018, vol. 45, no. 4, pp. 469-476. doi: 10.1007/s11033-018-4182-z
  71. Nair V.R., Franco L.H., Zacharia V.M., Khan H.S., Stamm C.E., You W., Marciano D.K., Yagita H., Levine B., Shiloh M.U. Microfold cells actively translocate Mycobacterium tuberculosis to initiate infection. Cell Rep., 2016, vol. 16, no. 5, pp. 1253-1258. doi: 10.1016/j.celrep.2016.06.080
  72. Nigou J., Zelle-Rieser C., Gilleron M., Thurnher M., Puzo G. Mannosylated lipoarabinomannans inhibit IL-12 production by human dendritic cells: evidence for a negative signal delivered through the mannose receptor. J. Immunol., 2001, vol. 166, no. 12, pp. 7477-7485. doi: 10.4049/jimmunol.166.12.7477
  73. Pattison M.J., Mitchell O., Flynn H.R., Chen C.-S., Yang H.-T., Ben-Addi H., Boeing S., Snijders A.P., Ley S.C. TLR and TNF-R1 activation of the MKK3/MKK6-p38a axis in macrophages is mediated by TPL-2 kinase. Biochem. J, 2016, vol. 473, no. 18, pp. 2845-2861. doi: 10.1042/BCJ20160502
  74. Peterson P.K., Gekker G., Hu S., Sheng W.S., Anderson W.R., Ulevitch R.J., Tobias P.S., Gustafson K.V., Molitor T.W., Chao C.C. CD14 receptor-mediated uptake of nonopsonized Mycobacterium tuberculosis by human microglia. Infect. Immun., 1995, vol. 63, no. 4, pp. 1598-1602
  75. Platz J., Beisswenger C., Dalpke A., Koczulla R., Pinkenburg O., Vogelmeier C., Bals R. Microbial DNA induces a host defense reaction of human respiratory epithelial cells. J. Immunol., 2004, vol. 173, no. 2, pp. 1219-1223. doi: 10.4049/jimmunol.173.2.1219
  76. Prabha C., Rajashree P., Sulochana D.D. TLR2 and TLR4 expression on the immune cells of tuberculous pleural fluid. Immunol. Lett., 2008, vol. 117, no. 1, pp. 26-34. doi: 10.1016/j.imlet.2007.11.002
  77. Poyhonen L., Kroger L., Huhtala H., Makinen J., Nuolivirta K., Mertsola J., He Q., Korppi M. Association of MBL2, TLR1, TLR2 and TLR6 polymorphisms with production of IFN-y and IL-12 in BCG osteitis survivors R1. Pediatr. Infect. Dis. J, 2017, vol. 36, no. 2,pp. 135-139. doi: 10.1097/INF.0000000000001375
  78. Queiroz A., Riley L.W. Bacterial immunostat: Mycobacterium tuberculosis lipids and their role in the host immune response. Rev. Soc. Bras. Med. Trop, 2017, vol. 50, no. 1,pp. 9-18. doi: 10.1590/0037-8682-0230-2016
  79. Quesniaux V., Fremond C., Jacobs M., Parida S., Nicolle D., Yeremeev V., Bihl F., Erard F., Botha T., Drennan M., Soler M.N., Le Bert M., Schnyder B., Ryffel B. Toll-like receptor pathways in the immune responses to mycobacteria. Microbes Infect., 2004, vol. 6, no. 10, pp. 946-959. doi: 10.1016/j.micinf.2004.04.016
  80. Ramakrishna K., Premkumar K., Kabeerdoss J., John K.R. Impaired toll like receptor 9 response in pulmonary tuberculosis. Cytokine, 2017, vol. 90, pp. 38-43. doi: 10.1016/j.cyto.2016.10.006
  81. Richardson E.T., Shukla S., Sweet D.R., Wearsch P.A., Tsichlis P.N., Boom W.H., Harding C. V. Toll-like receptor 2-dependent extracellular signal-regulated kinase signaling in Mycobacterium tuberculosis-infected macrophages drives anti-inflammatory responses and inhibits Th1 polarization of responding T cells. Infect. Immun., 2015, vol. 83, no. 6, pp. 2242-2254. doi: 10.1128/iai.00135-15
  82. Rivas-Santiago B., Contreras J.C.L., Sada E., Hernandez-Pando R. The potential role of lung epithelial cells and P-defensins in experimental latent tuberculosis. Scand. J. Immunol., 2008, vol. 67, no. 5, pp. 448-452. doi: 10.1111/j.1365-3083.2008.02088.x
  83. Rivas-Santiago B., Hernandez-Pando R., Carranza C., Juarez E., Contreras J.L., Aguilar-Leon D., Torres M., Sada E. Expression of cathelicidin LL-37 during Mycobacterium tuberculosis infection in human alveolar macrophages, monocytes, neutrophils, and epithelial cells. Infect. Immun., 2008, vol. 76, no. 3, pp. 935—941. doi: 10.1128/IAI.01218-07
  84. Rocha-Ramfrez L.M., Estrada-Garcfa I., Lopez-Marfn L.M., Segura-Salinas E., Mendez-Aragon P., Soolingen D. Van, Torres-Gonzalez R., Chacon-Salinas R., Estrada-Parra S., Maldonado-Bernal C., Lopez-Macfas C., Isibasi A. Mycobacterium tuberculosis lipids regulate cytokines, TLR-2/4 and MHC class II expression in human macrophages. Tuberculosis, 2008, vol. 88, no. 3, pp. 212-220. doi: 10.1016/J.TUBE.2007.10.003
  85. Rothfuchs A.G., Bafica A., Feng C.G., Egen J.G., Williams D.L., Brown G.D., Sher A. Dectin-1 interaction with Mycobacterium tuberculosis leads to enhanced IL-12p40 production by splenic dendritic cells. J. Immunol., 2007, vol. 179, no. 6, pp. 3463-3471. doi: 10.4049/jimmunol.179.6.3463
  86. Saavedra R., Segura E., Leyva R., Esparza L.A., Lopez-Marfn L.M. Mycobacterial di-O-acyl-trehalose inhibits mitogen-and antigen-induced proliferation of murine T cells in vitro. Clin. Diagn. Lab. Immunol., 2001, vol. 8, no. 6, pp. 1081-1088. doi: 10.1128/CDLI.8.6.1-91-1088.2001
  87. Sakamoto K., Kim M.J., Rhoades E.R., Allavena R.E., Ehrt S., Wainwright H.C., Russell D.G., Rohde K.H. Mycobacterial trehalose dimycolate reprograms macrophage global gene expression and activates matrix metalloproteinases. Infect. Immun., 2013, vol. 81, no. 3,pp. 764-776. doi: 10.1128/IAI.00906-12
  88. Schlesinger L.S., Azad A.K., Torrelles J.B., Roberts E. Determinants of phagocytosis, phagosome biogenesis and autophagy for Mycobacterium tuberculosis. In: Handbook of tuberculosis. Immunology and cell biology. Eds: Kaufmann S.H.E., Britton W.J. Wiley-VCH Verlag; Weinheim, Germany: 2008. pp. 1-22.
  89. Schlesinger L., Torrelles J., Azad A., Henning L., Carlson T. Role of C-type lectins in Mycobacterial infections. Curr. Drug Targets, 2008, vol. 9, no. 2, pp. 102-112. doi: 10.2174/138945008783502467
  90. Schurz H., Daya M., Moller M., Hoal E.G., Salie M. TLR1, 2, 4, 6 and 9 variants associated with tuberculosis susceptibility: a systematic review and meta-analysis. PLoS One, 2015, vol. 10, no. 10: e0139711. doi: 10.1371/journal.pone.0139711
  91. Selvaraj P., Jawahar M.S., Rajeswari D.N., Alagarasu K., Vidyarani M., Narayanan P.R. Role of mannose binding lectin gene variants on its protein levels and macrophage phagocytosis with live Mycobacterium tuberculosis in pulmonary tuberculosis. FEMS Immunol. Med. Microbiol., 2006, vol. 46, no. 3,pp. 433-437. doi: 10.1111/j.1574-695X.2006.00053.x
  92. Sepehri Z., Kiani Z., Kohan F., Ghavami S. Toll-like receptor 4 as an immune receptor against Mycobacterium tuberculosis: a systematic review. Lab. Med., 2018. doi: 10.1093/labmed/lmy047
  93. Sequeira P.C., Senaratne R.H., Riley L.W. Inhibition of toll-like receptor 2 (TLR-2)-mediated response in human alveolar epithelial cells by mycolic acids and Mycobacterium tuberculosis mce1 operon mutant. Pathog. Dis., 2014, vol. 70, no. 2, pp. 132-140. doi: 10.1111/2049-632X.12110
  94. Sever-Chroneos Z., Tvinnereim A., Hunter R.L., Chroneos Z.C. Prolonged survival of scavenger receptor class A-deficient mice from pulmonary Mycobacterium tuberculosis infection. Tuberculosis (Edinb.), 2011, vol. 91, suppl. 1, pp. S69-S74. doi: 10.1016/
  95. Shin D.M., Yuk J.M., Lee H.M., Lee S.H., Son J.W., Harding C. V., Kim J.M., Modlin R.L., Jo E.K. Mycobacterial lipoprotein activates autophagy via TLR2/1/CD14 and a functional vitamin D receptor signalling. Cell. Microbiol., 2010, vol. 12, no. 11, pp. 1648-1665. doi: 10.1111/j.1462-5822.2010.01497.x
  96. Soeroto A.Y., Dahlan Z., Kartasasmita C.B., Parwati I. Association between Arg753Gln and Arg677Trp polymorphisms of TLR2 gene with active pulmonary tuberculosis in an indonesian population. Acta Med. Indones., 2018, vol. 50, no. 1, pp. 53—60.
  97. Sorensen G.L. Surfactant protein D in respiratory and non-respiratory diseases. Front. Med., 2018, vol. 5, no. 18. doi: 10.3389/fmed.2018.00018
  98. Srivastava V., Manchanda M., Gupta S., Singla R., Behera D., Das G., Natarajan K. Toll-like receptor 2 and DC-SIGNR1 differentially regulate suppressors of cytokine signaling 1 in dendritic cells during Mycobacterium tuberculosis infection. J. Biol. Chem., 2009, vol. 284, no. 38,pp. 25532-25541. doi: 10.1074/jbc.M109.006221
  99. Suzuki T., Chow C., Downey G.P. Role of innate immune cells and their products in lung immunopathology. Int. J. Biochem. Cell Biol, 2008, vol. 40, no. 6-7, pp. 1348-1361. doi: 10.1016/j.biocel.2008.01.003
  100. Soborg C., Madsen H.O., Andersen A.B., Lillebaek T., Kok-Jensen A., Garred P. Mannose-binding lectin polymorphisms in clinical tuberculosis. J. Infect. Dis., 2003, vol. 188, no. 5, pp. 777-782. doi: 10.1086/377183
  101. Tailleux L., Pham-Thi N., Bergeron-Lafaurie A., Herrmann J.L., Charles P., Schwartz O., Scheinmann P., Lagrange P.H., De Blic J., Tazi A., Gicquel B., Neyrolles O. DC-SIGN induction in alveolar macrophages defines privileged target host cells for mycobacteria in patients with tuberculosis. PLoS Med, 2005, vol. 2, no. 12, pp. 1269-1279. doi: 10.1371/journal.pmed.0020381
  102. Tailleux L., Schwartz O., Herrmann J.-L., Pivert E., Jackson M., Amara A., Legres L., Dreher D., Nicod L.P., Gluckman J.C., Lagrange P.H., Gicquel B., Neyrolles O. DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells. J. Exp. Med, 2003, vol. 197, no. 1, pp. 121-127. doi: 10.1084/jem.20021468
  103. Takeuchi O., Sato S., Horiuchi T., Hoshino K., Takeda K., Dong Z., Modlin R.L., Akira S. Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J. Immunol., 2002, vol. 169, no. 1, pp. 10-14. doi: 10.4049/jimmu-nol.169.1.10
  104. Torrelles J.B., Azad A.K., Schlesinger L.S. Fine discrimination in the recognition of individual species of phosphatidyl-myoinositol mannosides from Mycobacterium tuberculosis by C-type lectin pattern recognition receptors. J. Immunol., 2006, vol. 177, no. 3, pp. 1805-1816. doi: 10.4049/jimmunol.177.3.1805
  105. Udgata A., Qureshi R., Mukhopadhyay S. Transduction of functionally contrasting signals by two mycobacterial PPE proteins downstream of TLR2 receptors. J. Immunol., 2016, vol. 197, no. 5, pp. 1776-1787. doi: 10.4049/jimmunol.1501816
  106. Van der Veerdonk F.L., Teirlinck A.C., Kleinnijenhuis J., Kullberg B.J., van Crevel R., van der Meer J.W.M., Joosten L.A.B., Netea M.G. Mycobacterium tuberculosis induces IL-17A responses through TLR4 and dectin-1 and is critically dependent on endogenous IL-1. J. Leukoc. Biol., 2010, vol. 88, no. 2, pp. 227-232. doi: 10.1189/jlb.0809550
  107. Villeneuve C., Gilleron M., Maridonneau-Parini I., Daffe M., Astarie-Dequeker C., Etienne G. Mycobacteria use their surface-exposed glycolipids to infect human macrophages through a receptor-dependent process. J. Lipid Res., 2005, vol. 46, no. 3, pp. 475-483. doi: 10.1194/jlr.M400308-JLR200
  108. Wieland C.W., van der Windt G.J.W., Wiersinga W.J., Florquin S., van der Poll T. CD14 contributes to pulmonary inflammation and mortality during murine tuberculosis. Immunology, 2008, vol. 125, no. 2, pp. 272-279. doi: 10.1111/j.1365-2567.2008.02840.x
  109. Wright J.R. Immunoregulatory functions of surfactant proteins. Nat. Rev. Immunol., 2005, vol. 5, no. 1, pp. 58- 68. doi: 10.1038/nri1528
  110. Wu S., Huang W., Wang D., Wang Y., Wang M., Zhang M., He J.-Q. Evaluation of TLR 2, TLR 4, and TOLLIP polymorphisms for their role in tuberculosis susceptibility. Apmis, 2018, vol. 126, no. 6, pp. 501-508. doi: 10.1111/apm.12855
  111. Xu Q., Jin M.M., Zheng W.W., Zhu L., Xu S.L. Role of Toll-like receptor 2/4-nuclear factor-KB signaling pathway in invasion of Mycobacterium tuberculosis to mouse dendritic cells. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2014, vol. 43, no. 2, pp. 200-206.
  112. Xue Y., Zhao Z.Q., Chen F., Zhang L., Li G.D., Ma K.W., Bai X.F., Zuo Y.J. Polymorphisms in the promoter of the CD14 gene and their associations with susceptibility to pulmonary tuberculosis. Tissue Antigens, 2012, vol. 80, no. 5, pp. 437-443. doi: 10.1111/j.1399-0039.2012.01958.x
  113. Yadav M., Schorey J.S. The P-glucan receptor dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria. Blood, 2006, vol. 108, no. 9, pp. 3168-3175. doi: 10.1182/blood-2006-05-024406
  114. Yang C.-S., Shin D.-M., Kim K.-H., Lee Z.-W., Lee C.-H., Park S.G., Bae Y.S., Jo E.-K. NADPH oxidase 2 interaction with TLR2 is required for efficient innate immune responses to mycobacteria via cathelicidin expression. J. Immunol., 2009, vol. 182, no. 6, pp. 3696-705. doi: 10.4049/jimmunol.0802217
  115. Yang Y., Kulka K., Montelaro R.C., Reinhart T.A., Sissons J., Aderem A., Ojha A.K. A hydrolase of trehalose dimycolate induces nutrient influx and stress sensitivity to balance intracellular growth of Mycobacterium tuberculosis. Cell Host Microbe, 2014, vol. 15, no. 2, pp. 153-163. doi: 10.1016/j.chom.2014.01.008
  116. Zenaro E., Donini M., Dusi S. Induction of Th1/Th17 immune response by Mycobacterium tuberculosis: role of dectin-1, mannose receptor, and DC-SIGN. J. Leukoc. Biol., 2009, vol. 86, no. 6, pp. 1393-1401. doi: 10.1189/jlb.0409242
  117. Zhao L., Liu K., Kong X., Tao Z., Wang Y., Liu Y. Association of polymorphisms in Toll-like receptors 4 and 9 with risk of pulmonary tuberculosis: a meta-analysis. Med. Sci. Monit., 2015, vol. 21, pp. 1097-1106. doi: 10.12659/MSM.893755
  118. Zimmermann N., Saiga H., Houthuys E., Moura-Alves P., Koehler A., Bandermann S., Dorhoi A., Kaufmann S.H.E. Syndecans promote mycobacterial internalization by lung epithelial cells. Cell. Microbiol., 2016, vol. 18, no. 12, pp. 1846-1856. doi: 10.1111/cmi.12627z

Supplementary files

There are no supplementary files to display.

Copyright (c) 2020 Lapshtaeva A.V., Zhivechkova E.A., Sychev I.V., Evsegneeva I.V., Novikov V.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 64788 от 02.02.2016.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies