• Development of immune response in pneumonia caused by Klebsiella pneumoniae. Рart 4

Development of immune response in pneumonia caused by Klebsiella pneumoniae. Рart 4

SOVREMENNAYA PEDIATRIYA.2017.8(88):50-58; doi 10.15574/SP.2017.88.50

Abaturov O. E., Nikulina A. O.
SI «Dnіpropetrovsk Medical Academy of Health Ministry of Ukraine», Dnipro, Ukraine

The article, based on literary sources, demonstrates the role of cellular reactions in the development of the immune response in pneumonia caused by Klebsiella pneumoniae. The features of cellular response of the immune system in the pulmonary tissue in case of infection caused by Klebsiella, the mechanisms of recruitment and activation of proinflammatory immunocytes, and the processes of the bacterial killing, which provide effective sanogenesis in pneumonia of Klebsiella aetiology, are described in the article.
Key words: pneumonia, Klebsiella pneumoniae, bacterial clearance, immunocytes.


1. Fear VS, Lai SP, Zosky GR et al. (2016). A pathogenic role for the integrin CD103 in experimental allergic airways diseaseю Physiol Rep. 4(21): pii: e13021. https://doi.org/10.14814/phy2.13021.

2. Broug-Holub E, Toews GB, van Iwaarden JF et al. (1997). Alveolar macrophages are required for protective pulmonary defenses in murine Klebsiella pneumonia: elimination of alveolar macrophages increases neutrophil recruitment but decreases bacterial clearance and survival. Infect Immun. 65(4): 1139—46. PMid:9119443 PMCid:PMC175109.

3. Beaty SR, Rose JrCE, Sung SS. (2007). Diverse and potent chemokine production by lung CD11bhigh dendritic cells in homeostasis and in allergic lung inflammation. J Immunol. 178(3): 1882—95. https://doi.org/10.4049/jimmunol.178.3.1882.

4. Becher B, Tugues S, Greter M. (2016). GM-CSF: From Growth Factor to Central Mediator of Tissue Inflammation. Immunity. 45(5): 963—973. https://doi.org/10.1016/j.immuni.2016.10.026.

5. Belaaouaj A. (2002). Neutrophil elastase-mediated killing of bacteria: lessons from targeted mutagenesis. Microbes Infect. 4(12): 1259—64. https://doi.org/10.1016/S1286-4579(02)01654-4.

6. Zelante T, Wong AY, Ping TJ et al. (2015). CD103(+) Dendritic Cells Control Th17 Cell Function in the Lung. Cell Rep. 12(11): 1789—801. https://doi.org/10.1016/j.celrep.2015.08.030.

7. Schurr JR, Young E, Byrne P et al. (2005). Central role of toll-like receptor 4 signaling and host defense in experimental pneumonia caused by Gram-negative bacteria. Infect Immun. 73(1): 532—45. https://doi.org/10.1128/IAI.73.1.532-545.2005.

8. Collin M, McGovern N, Haniffa M. (2013). Human dendritic cell subsets. Immunology. 140(1): 22—30. https://doi.org/10.1111/imm.12117.

9. Xu X, Weiss ID, Zhang HH et al. (2014). Conventional NK cells can produce IL-22 and promote host defense in Klebsiella pneumoniae pneumonia. J Immunol. 192(4): 1778—86. https://doi.org/10.4049/jimmunol.1300039.

10. Cook PC, MacDonald AS. (2016). Dendritic cells in lung immunopathology. Semin Immunopathol. 38(4): 449—60. https://doi.org/10.1007/s00281-016-0571-3.

11. Cortez VS, Robinette ML, Colonna M. (2015). Innate lymphoid cells: new insights into function and development. Curr Opin Immunol. 32: 71—7. https://doi.org/10.1016/j.coi.2015.01.004.

12. Hao S, Han X, Wang D et al. (2016). Critical role of CCL22/CCR4 axis in the maintenance of immune homeostasis during apoptotic cell clearance by splenic CD8α(+) CD103(+) dendritic cells. Immunology. 148(2): 174—86. https://doi.org/10.1111/imm.12596.

13. Alloatti A, Kotsias F, Magalhaes JG, Amigorena S. (2016). Dendritic cell maturation and cross-presentation: timing matters! Immunol Rev. 272(1): 97—108. https://doi.org/10.1111/imr.12432.

14. Del Rio ML, Bernhardt G, Rodriguez-Barbosa JI, Forster R. (2010). Development and functional specialization of CD103+ dendritic cells. Immunol Rev. 234(1); 268—81. https://doi.org/10.1111/j.0105-2896.2009.00874.x; PMid:20193025.

15. Webster SJ, Daigneault M, Bewley MA et al. (2010). Distinct cell death programs in monocytes regulate innate responses following challenge with common causes of invasive bacterial disease. J Immunol. 185(5): 2968—79. https://doi.org/10.4049/jimmunol.1000805.

16. Xiong H, Carter RA, Leiner IM et al. (2015). Distinct Contributions of Neutrophils and CCR2+ Monocytes to Pulmonary Clearance of Different Klebsiella pneumoniae Strains. Infect Immun. 83(9): 3418—27. https://doi.org/10.1128/IAI.00678-15.

17. Happel KI, Dubin PJ, Zheng M et al. (2005). Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumonia. J Exp Med. 202(6): 761—9. https://doi.org/10.1084/jem.20050193.

18. Dominguez PM, Ardavin C. (2010). Differentiation and function of mouse monocyte-derived dendritic cells in steady state and inflammation. Immunol Rev. 234(1): 90—104. https://doi.org/10.1111/j.0105-2896.2009.00876.x.

19. Collins CB, Aherne CM, McNamee EN et al. (2012). Flt3 ligand expands CD103+ dendritic cells and FoxP3+ T regulatory cells, and attenuates Crohn's-like murine ileitis. Gut. 61(8): 1154—62. https://doi.org/10.1136/gutjnl-2011-300820.

20. Gargett T, Christo SN, Hercus TR et al. (2016). GM-CSF signalling blockade and chemotherapeutic agents act in concert to inhibit the function of myeloid-derived suppressor cells in vitro. Clin Transl Immunology. 5(12): e119. https://doi.org/10.1038/cti.2016.80.

21. Garcia-Laorden MI, Stroo I, Blok DC et al. (2016). Granzymes A and B Regulate the Local Inflammatory Response during Klebsiella pneumoniae Pneumonia. J Innate Immun. 8(3): 258—68. https://doi.org/10.1159/000443401.

22. Guilliams M, Lambrecht BN, Hammad H. (2013). Division of labor between lung dendritic cells and macrophages in the defense against pulmonary infections. Mucosal Immunol. 6(3): 464—73. https://doi.org/10.1038/mi.2013.14.

23. Chen L, Zhang Z, Barletta KE et al. (2013). Heterogeneity of lung mononuclear phagocytes during pneumonia: contribution of chemokine receptors. Am J Physiol Lung Cell Mol Physiol. 305(10): 702—11. https://doi.org/10.1152/ajplung.00194.2013.

24. Van Beek JJ, Gorris MA, Skold AE et al. (2016). Human blood myeloid and plasmacytoid dendritic cells cross activate each other and synergize in inducing NK cell cytotoxicity. Oncoimmunology. 5(10): e1227902. https://doi.org/10.1080/2162402X.2016.1227902.

25. Cui TX, Maheshwer B, Hong JY et al. (2016). Hyperoxic Exposure of Immature Mice Increases the Inflammatory Response to Subsequent Rhinovirus Infection: Association with Danger Signals. J Immunol. 196(11): 4692—705. https://doi.org/10.4049/jimmunol.1501116.

26. Demedts IK, Brusselle GG, Vermaelen KY, Pauwels RA. (2005). Identification and characterization of human pulmonary dendritic cells. Am J Respir Cell Mol Biol. 32(3): 177—84. https://doi.org/10.1165/rcmb.2004-0279OC; PMid:15576669.

27. Soudja SM, Ruiz AL, Marie JC, Lauvau G. (2012). Inflammatory monocytes activate memory CD8(+) T and innate NK lymphocytes independent of cognate antigen during microbial pathogen invasion. Immunity. 37(3): 549—62. https://doi.org/10.1016/j.immuni.2012.05.029.

28. Liang J, Huang HI, Benzatti FP et al. (2016). Inflammatory Th1 and Th17 in the Intestine Are Each Driven by Functionally Specialized Dendritic Cells with Distinct Requirements for MyD88. Cell Rep. 17(5): 1330—1343. https://doi.org/10.1016/j.celrep.2016.09.091.

29. Parker D, Ahn D, Cohen T, Prince A. (2016). Innate Immune Signaling Activated by MDR Bacteria in the Airway. Physiol Rev. 96(1): 19—53. https://doi.org/10.1152/physrev.00009.2015.

30. Xiong H, Keith JW, Samilo DW et al. (2016). Innate Lymphocyte/Ly6C(hi) Monocyte Crosstalk Promotes Klebsiella Pneumoniae Clearance. Cell. 165(3): 679—89. https://doi.org/10.1016/j.cell.2016.03.017.

31. Martin B, Hirota K, Cua DJ et al. (2009). Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals. Immunity. 31(2): 321—30. https://doi.org/10.1016/j.immuni.2009.06.020.

32. Batra S, Cai S, Balamayooran G, Jeyaseelan S. (2012). Intrapulmonary administration of leukotriene B(4) augments neutrophil accumulation and responses in the lung to Klebsiella infection in CXCL1 knockout mice. J Immunol. 188(7): 3458—68. https://doi.org/10.4049/jimmunol.1101985.

33. Ivanov S, Fontaine J, Paget C et al. (2012). Key role for respiratory CD103(+) dendritic cells, IFN-γ, and IL-17 in protection against Streptococcus pneumoniae infection in response to α-galactosylceramide. J Infect Dis. 206(5): 723—34. https://doi.org/10.1093/infdis/jis413.

34. Kim TH, Lee HK. (2014). Differential roles of lung dendritic cell subsets against respiratory virus infection. Immune Netw. —— Vol.14(3). — P.128—37. doi 10.4110/in.2014.14.3.128.

35. Wang J, Li F, Sun R et al. (2014). Klebsiella pneumoniae alleviates influenza-induced acute lung injury via limiting NK cell expansion. J Immunol. 193(3): 1133—41. https://doi.org/10.4049/jimmunol.1303303.

36. Van Elssen CH, Vanderlocht J, Frings PW et al. (2010). Klebsiella pneumoniae-triggered DC recruit human NK cells in a CCR5-dependent manner leading to increased CCL19-responsiveness and activation of NK cells. Eur J Immunol. 40(11): 3138—49. https://doi.org/10.1002/eji.201040496.

37. Kopf M, Schneider C, Nobs SP. (2015). The development and function of lung-resident macrophages and dendritic cells. Nat Immunol. 16(1): 36—44. https://doi.org/10.1038/ni.3052.

38. Lodoen MB, Lanier LL. (2006). Natural killer cells as an initial defense against pathogens. Curr Opin Immunol. 18(4): 391—8. https://doi.org/10.1016/j.coi.2006.05.002.

39. El Rayes T, Catena R, Lee S et al. (2015). Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1. Proc Natl Acad Sci USA. 112(52): 16000—5. https://doi.org/10.1073/pnas.1507294112.

40. Hackstein H, Kranz S, Lippitsch A et al. (2013). Modulation of respiratory dendritic cells during Klebsiella pneumonia infection. Respir Res. 14: 91. https://doi.org/10.1186/1465-9921-14-91.

41. Morita H, Moro K, Koyasu S. (2016). Innate lymphoid cells in allergic and nonallergic inflammation. J Allergy Clin Immunol. 138(5): 1253—1264. https://doi.org/10.1016/j.jaci.2016.09.011.

42. Furuhashi K, Suda T, Hasegawa H et al. (2012). Mouse lung CD103+ and CD11bhigh dendritic cells preferentially induce distinct CD4+ T-cell responses. Am J Respir Cell Mol Biol. 46(2): 165-72. https://doi.org/10.1165/rcmb.2011-0070OC.

43. Hirche TO, Gaut JP, Heinecke JW, Belaaouaj A. (2005). Myeloperoxidase plays critical roles in killing Klebsiella pneumoniae and inactivating neutrophil elastase: effects on host defense. J Immunol. 174(3): 1557—65. https://doi.org/10.4049/jimmunol.174.3.1557.

44. Dollery CM, Owen CA, Sukhova GK et al. (2003). Neutrophil elastase in human atherosclerotic plaques: production by macrophages. Circulation. 107(22): 2829—36. https://doi.org/10.1161/01.CIR.0000072792.65250.4A.

45. Branzk N, Lubojemska A, Hardison SE et al. (2014). Neutrophils sense microbe size and selectively release neutrophil extracellular traps in response to large pathogens. Nat Immunol. 15(11): 1017—25. https://doi.org/10.1038/ni.2987.

46. Goldszmid RS, Caspar P, Rivollier A et al. (2012). NK cell-derived interferon-γ orchestrates cellular dynamics and the differentiation of monocytes into dendritic cells at the site of infection. Immunity. 36(6): 1047—59. https://doi.org/10.1016/j.immuni.2012.03.026.

47. Odobasic D, Kitching AR, Holdsworth SR. (2016). Neutrophil-Mediated Regulation of Innate and Adaptive Immunity: The Role of Myeloperoxidase. J Immunol Res. 2016: 2349817. https://doi.org/10.1155/2016/2349817.

48. Paczosa MK, Mecsas J. (2016). Klebsiella pneumoniae: Going on the Offense with a Strong Defense. Microbiol Mol Biol Rev. 80(3): 629—61. https://doi.org/10.1128/MMBR.00078-15.

49. Malloy AM, Ruckwardt TJ, Morabito KM et al. (2017). Pulmonary Dendritic Cell Subsets Shape the Respiratory Syncytial Virus-Specific CD8+ T Cell Immunodominance Hierarchy in Neonates. J Immunol. 198(1): 394—403. https://doi.org/10.4049/jimmunol.1600486.

50. Quezada A, Maggi L, Norambuena X et al. (2016). Response to pneumococcal polysaccharide vaccine in children with asthma, and children with recurrent respiratory infections, and healthy children. Allergol Immunopathol (Madr). 44(4): 376—81. https://doi.org/10.1016/j.aller.2016.01.003.

51. Robinette ML, Colonna M. (2016). Immune modules shared by innate lymphoid cells and T cells. J Allergy Clin Immunol. 138(5): 1243—1251. https://doi.org/10.1016/j.jaci.2016.09.006.

52. Rosler B, Herold S. (2016). Lung epithelial GM-CSF improves host defense function and epithelial repair in influenza virus pneumonia – a new therapeutic strategy? Mol Cell Pediatr. 3(1): 29. https://doi.org/10.1186/s40348-016-0055-5.

53. Sabado RL, Balan S, Bhardwaj N. (2017). Dendritic cell-based immunotherapy. Cell Res. 27(1): 74—95. https://doi.org/10.1038/cr.2016.157.

54. Schlitzer A, Ginhoux F. (2014). Organization of the mouse and human DC network. Curr Opin Immunol. 26: 90—9. https://doi.org/10.1016/j.coi.2013.11.002.

55. Sprangers S, de Vries TJ, Everts V. (2016). Monocyte Heterogeneity: Consequences for Monocyte-Derived Immune Cells. J Immunol Res. 2016: 1475435. https://doi.org/10.1155/2016/1475435.

56. Bloodworth MH, Newcomb DC, Dulek DE et al. (2016). STAT6 Signaling Attenuates Interleukin-17-Producing γδ T Cells during Acute Klebsiella pneumoniae Infection. Infect Immun. 84(5): 1548—55. https://doi.org/10.1128/IAI.00646-15.

57. Sutton CE, Mielke LA, Mills KH. (2012). IL-17-producing γδ T cells and innate lymphoid cells. Eur J Immunol. 42(9): 2221—31. https://doi.org/10.1002/eji.201242569.

58. Tait Wojno ED, Artis D. (2016). Emerging concepts and future challenges in innate lymphoid cell biology. J Exp Med. 213(11): 2229—2248. https://doi.org/10.1084/jem.20160525.

59. Olivar R, Luque A, Cardenas-Brito S et al. (2016). The Complement Inhibitor Factor H Generates an Anti-Inflammatory and Tolerogenic State in Monocyte-Derived Dendritic Cells. J Immunol. 196(10): 4274—90. https://doi.org/10.4049/jimmunol.1500455.

60. Merad M, Sathe P, Helft J et al. (2013). The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol. 31: 563—604. https://doi.org/10.1146/annurev-immunol-020711-074950.

61. Zhao Y, Olonisakin TF, Xiong Z et al. (2015). Thrombospondin-1 restrains neutrophil granule serine protease function and regulates the innate immune response during Klebsiella pneumoniae infection. Mucosal Immunol. 8(4): 896—905. https://doi.org/10.1038/mi.2014.120.

62. Chen K, Wang JM, Yuan R et al. (2016). Tissue-resident dendritic cells and diseases involving dendritic cell malfunction. Int Immunopharmacol. 34: 1—15. https://doi.org/10.1016/j.intimp.2016.02.007.

63. Standiford LR, Standiford TJ, Newstead MJ et al. (2012). TLR4-dependent GM-CSF protects against lung injury in Gram-negative bacterial pneumonia. Am J Physiol Lung Cell Mol Physiol. 302(5): 447—54. https://doi.org/10.1152/ajplung.00415.2010.

64. Murakami T, Hatano S, Yamada H et al. (2016). Two Types of Interleukin 17A-Producing γδ T Cells in Protection Against Pulmonary Infection With Klebsiella pneumoniae. J Infect Dis. 214(11): 1752—1761. https://doi.org/10.1093/infdis/jiw443; PMid:27651419

65. Upham JW, Xi Y. (2016). Dendritic cells in human lung disease: recent advances. Chest. pii: S0012-3692(16)59355-6..

66. Van der Aa. E, van Montfoort N, Woltman AM. (2015). BDCA3(+)CLEC9A(+) human dendritic cell function and development. Semin Cell Dev Biol. 41: 39—48. https://doi.org/10.1016/j.semcdb.2014.05.016.

67. Webster B, Assil S, Dreux M. (2016). Cell-Cell Sensing of Viral Infection by Plasmacytoid Dendritic Cells. J Virol. 90(22): 10050—10053. https://doi.org/10.1128/JVI.01692-16.

68. Xiong H, Pamer EG. (2015). Monocytes and infection: modulator, messenger and effector. Immunobiology. 220(2): 210—4. https://doi.org/10.1016/j.imbio.2014.08.007.

69. Zhang Z, Wang FS. (2005). Plasmacytoid dendritic cells act as the most competent cell type in linking antiviral innate and adaptive immune responses. Cell Mol Immunol. 2(6): 411—7. PMid:16426490.