#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Border Patrol Gone Awry: Lung NKT Cell Activation by Exacerbates Tularemia-Like Disease


NKT cells are innate-like lymphocytes with a demonstrated role in a wide range of diseases. Often cited for their ability to rapidly produce a variety of cytokines upon activation, they have long been appreciated for their ability to “jump-start” the immune system and to shape the quality of both the innate and adaptive response. This understanding of their function has been deduced from in vitro experiments or through the in vivo administration of highly potent, chemically synthesized lipid ligands, which may not necessarily reflect a physiologically relevant response as observed in a natural infection. Using a mouse model of pulmonary tularemia, we report that intranasal infection with the live vaccine strain of F. tularensis rapidly activates NKT cells and promotes systemic inflammation, increased tissue damage, and a dysregulated immune response resulting in increased morbidity and mortality in infected mice. Our data highlight the detrimental effects of NKT cell activation and identify a potential new target for therapies against pulmonary tularemia.


Vyšlo v časopise: Border Patrol Gone Awry: Lung NKT Cell Activation by Exacerbates Tularemia-Like Disease. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004975
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004975

Souhrn

NKT cells are innate-like lymphocytes with a demonstrated role in a wide range of diseases. Often cited for their ability to rapidly produce a variety of cytokines upon activation, they have long been appreciated for their ability to “jump-start” the immune system and to shape the quality of both the innate and adaptive response. This understanding of their function has been deduced from in vitro experiments or through the in vivo administration of highly potent, chemically synthesized lipid ligands, which may not necessarily reflect a physiologically relevant response as observed in a natural infection. Using a mouse model of pulmonary tularemia, we report that intranasal infection with the live vaccine strain of F. tularensis rapidly activates NKT cells and promotes systemic inflammation, increased tissue damage, and a dysregulated immune response resulting in increased morbidity and mortality in infected mice. Our data highlight the detrimental effects of NKT cell activation and identify a potential new target for therapies against pulmonary tularemia.


Zdroje

1. Scanlon ST, Thomas SY, Ferreira CM, Bai L, Krausz T, et al. (2011) Airborne lipid antigens mobilize resident intravascular NKT cells to induce allergic airway inflammation. J Exp Med 208: 2113–2124. doi: 10.1084/jem.20110522 21930768

2. Paget C, Trottein F (2013) Role of type 1 natural killer T cells in pulmonary immunity. Mucosal Immunol 6: 1054–1067. doi: 10.1038/mi.2013.59 24104457

3. Coquet JM, Chakravarti S, Kyparissoudis K, McNab FW, Pitt LA, et al. (2008) Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4-NK1.1- NKT cell population. Proc Natl Acad Sci U S A 105: 11287–11292. doi: 10.1073/pnas.0801631105 18685112

4. Brennan PJ, Brigl M, Brenner MB (2013) Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions. Nat Rev Immunol 13: 101–117. doi: 10.1038/nri3369 23334244

5. Lee YJ, Holzapfel KL, Zhu J, Jameson SC, Hogquist KA (2013) Steady-state production of IL-4 modulates immunity in mouse strains and is determined by lineage diversity of iNKT cells. Nat Immunol 14: 1146–1154. doi: 10.1038/ni.2731 24097110

6. Lynch L, Michelet X, Zhang S, Brennan PJ, Moseman A, et al. (2015) Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of Treg cells and macrophages in adipose tissue. Nat Immunol 16: 85–95. doi: 10.1038/ni.3047 25436972

7. Sag D, Krause P, Hedrick CC, Kronenberg M, Wingender G (2014) IL-10-producing NKT10 cells are a distinct regulatory invariant NKT cell subset. J Clin Invest 124: 3725–3740. doi: 10.1172/JCI72308 25061873

8. Bendelac A, Savage PB, Teyton L (2007) The biology of NKT cells. Annu Rev Immunol 25: 297–336. 17150027

9. Van Kaer L (2005) α-Galactosylceramide therapy for autoimmune diseases: prospects and obstacles. Nat Rev Immunol 5: 31–42. 15630427

10. Parekh VV, Wu L, Olivares-Villagomez D, Wilson KT, Van Kaer L (2013) Activated invariant NKT cells control central nervous system autoimmunity in a mechanism that involves myeloid-derived suppressor cells. J Immunol 190: 1948–1960. doi: 10.4049/jimmunol.1201718 23345328

11. Leung B, Harris HW (2011) NKT cells: the culprits of sepsis? J Surg Res 167: 87–95. doi: 10.1016/j.jss.2010.09.038 21035139

12. Munford RS (2006) Severe sepsis and septic shock: the role of gram-negative bacteremia. Annu Rev Pathol 1: 467–496. 18039123

13. Van Kaer L, Parekh VV, Wu L (2013) Invariant natural killer T cells as sensors and managers of inflammation. Trends Immunol 34: 50–58. doi: 10.1016/j.it.2012.08.009 23017731

14. Tupin E, Kinjo Y, Kronenberg M (2007) The unique role of natural killer T cells in the response to microorganisms. Nat Rev Microbiol 5: 405–417. 17487145

15. Hall JD, Woolard MD, Gunn BM, Craven RR, Taft-Benz S, et al. (2008) Infected-host-cell repertoire and cellular response in the lung following inhalation of Francisella tularensis Schu S4, LVS, or U112. Infect Immun 76: 5843–5852. doi: 10.1128/IAI.01176-08 18852251

16. Law HT, Lin AE, Kim Y, Quach B, Nano FE, et al. (2011) Francisella tularensis uses cholesterol and clathrin-based endocytic mechanisms to invade hepatocytes. Sci Rep 1: 192. doi: 10.1038/srep00192 22355707

17. Bossi P, Garin D, Guihot A, Gay F, Crance JM, et al. (2006) Bioterrorism: management of major biological agents. Cell Mol Life Sci 63: 2196–2212. 16964582

18. Dennis DT, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, et al. (2001) Tularemia as a biological weapon: medical and public health management. JAMA 285: 2763–2773. 11386933

19. Foley JE, Nieto NC (2010) Tularemia. Vet Microbiol 140: 332–338. doi: 10.1016/j.vetmic.2009.07.017 19713053

20. Ellis J, Oyston PC, Green M, Titball RW (2002) Tularemia. Clin Microbiol Rev 15: 631–646. 12364373

21. Sjostedt A (2007) Tularemia: history, epidemiology, pathogen physiology, and clinical manifestations. Ann N Y Acad Sci 1105: 1–29. 17395726

22. Steiner DJ, Furuya Y, Metzger DW (2014) Host-pathogen interactions and immune evasion strategies in Francisella tularensis pathogenicity. Infect Drug Resist 7: 239–251. doi: 10.2147/IDR.S53700 25258544

23. D'Elia RV, Laws TR, Carter A, Lukaszewski R, Clark GC (2013) Targeting the "Rising DAMP" during a Francisella tularensis infection. Antimicrob Agents Chemother. E-pub ahead of print.

24. Cowley SC (2009) Editorial: Proinflammatory cytokines in pneumonic tularemia: too much too late? J Leukoc Biol 86: 469–470. doi: 10.1189/jlb.0309119 19720615

25. Crane DD, Griffin AJ, Wehrly TD, Bosio CM (2013) B1a Cells Enhance Susceptibility to Infection with Virulent Francisella tularensis via Modulation of NK/NKT Cell Responses. J Immunol 190: 2756–2766. doi: 10.4049/jimmunol.1202697 23378429

26. Cowley SC, Elkins KL (2011) Immunity to francisella. Front Microbiol 2: 26. doi: 10.3389/fmicb.2011.00026 21687418

27. Cui J, Shin T, Kawano T, Sato H, Kondo E, et al. (1997) Requirement for Valpha14 NKT cells in IL-12-mediated rejection of tumors. Science 278: 1623–1626. 9374462

28. Mendiratta SK, Martin WD, Hong S, Boesteanu A, Joyce S, et al. (1997) CD1d1 mutant mice are deficient in natural T cells that promptly produce IL-4. Immunity 6: 469–477. 9133426

29. Smiley ST, Kaplan MH, Grusby MJ (1997) Immunoglobulin E production in the absence of interleukin-4-secreting CD1-dependent cells. Science 275: 977–979. 9020080

30. Chen Y-H, Chiu NM, Mandal M, Wang N, Wang C-R (1997) Impaired NK1+ T Cell Development and Early IL-4 Production in CD1-Deficient Mice. Immunity 6: 459–467. 9133425

31. Conlan JW, Chen W, Bosio CM, Cowley SC, Elkins KL (2011) Infection of mice with Francisella as an immunological model. Curr Protoc Immunol Chapter 19: Unit 19 14.

32. Reed L, Muench H. (1938) A Simple Method of Estimating Fifty Per Cent Endpoints. American Journal of Hygiene 27: 493–497.

33. Kurtz SL, Foreman O, Bosio CM, Anver MR, Elkins KL (2013) Interleukin-6 Is Essential for Primary Resistance to Francisella tularensis Live Vaccine Strain Infection. Infect Immun 81: 585–597. doi: 10.1128/IAI.01249-12 23230288

34. Griffin AJ, Crane DD, Wehrly TD, Bosio CM (2015) Successful Protection against Tularemia in C57BL/6 Mice Is Correlated with Expansion of Francisella tularensis-Specific Effector T Cells. Clin Vaccine Immunol 22: 119–128. doi: 10.1128/CVI.00648-14 25410207

35. Malik M, Bakshi CS, McCabe K, Catlett SV, Shah A, et al. (2007) Matrix metalloproteinase 9 activity enhances host susceptibility to pulmonary infection with type A and B strains of Francisella tularensis. J Immunol 178: 1013–1020. 17202364

36. Bedel R, Matsuda JL, Brigl M, White J, Kappler J, et al. (2012) Lower TCR repertoire diversity in Traj18-deficient mice. Nat Immunol 13: 705–706. doi: 10.1038/ni.2347 22814339

37. Vahl JC, Heger K, Knies N, Hein MY, Boon L, et al. (2013) NKT Cell-TCR Expression Activates Conventional T Cells in Vivo, but Is Largely Dispensable for Mature NKT Cell Biology. PLoS Biol 11: e1001589. doi: 10.1371/journal.pbio.1001589 23853545

38. Thomas SY, Scanlon ST, Griewank KG, Constantinides MG, Savage AK, et al. (2011) PLZF induces an intravascular surveillance program mediated by long-lived LFA-1-ICAM-1 interactions. J Exp Med 208: 1179–1188. doi: 10.1084/jem.20102630 21624939

39. Anderson KG, Mayer-Barber K, Sung H, Beura L, James BR, et al. (2014) Intravascular staining for discrimination of vascular and tissue leukocytes. Nat Protoc 9: 209–222. doi: 10.1038/nprot.2014.005 24385150

40. Holzapfel KL, Tyznik AJ, Kronenberg M, Hogquist KA (2014) Antigen-Dependent versus-Independent Activation of Invariant NKT Cells during Infection. J Immunol 192: 5490–5498. doi: 10.4049/jimmunol.1400722 24813205

41. Slight SR, Monin L, Gopal R, Avery L, Davis M, et al. (2013) IL-10 Restrains IL-17 to Limit Lung Pathology Characteristics following Pulmonary Infection with Francisella tularensis Live Vaccine Strain. Am J Pathol 183: 1397–1404. doi: 10.1016/j.ajpath.2013.07.008 24007881

42. Jamieson AM, Pasman L, Yu S, Gamradt P, Homer RJ, et al. (2013) Role of tissue protection in lethal respiratory viral-bacterial coinfection. Science 340: 1230–1234. doi: 10.1126/science.1233632 23618765

43. Verhoeven D, Teijaro JR, Farber DL (2009) Pulse-oximetry accurately predicts lung pathology and the immune response during influenza infection. Virology 390: 151–156. doi: 10.1016/j.virol.2009.05.004 19493556

44. Ojeda SS, Wang ZJ, Mares CA, Chang TA, Li Q, et al. (2008) Rapid dissemination of Francisella tularensis and the effect of route of infection. BMC Microbiol 8: 215. doi: 10.1186/1471-2180-8-215 19068128

45. Bar-Haim E, Gat O, Markel G, Cohen H, Shafferman A, et al. (2008) Interrelationship between dendritic cell trafficking and Francisella tularensis dissemination following airway infection. PLoS Pathog 4: e1000211. doi: 10.1371/journal.ppat.1000211 19023422

46. Kingry LC, Troyer RM, Marlenee NL, Bielefeldt-Ohmann H, Bowen RA, et al. (2011) Genetic identification of unique immunological responses in mice infected with virulent and attenuated Francisella tularensis. Microbes Infect 13: 261–275. doi: 10.1016/j.micinf.2010.10.022 21070859

47. Sharma J, Li Q, Mishra BB, Pena C, Teale JM (2009) Lethal pulmonary infection with Francisella novicida is associated with severe sepsis. J Leukoc Biol 86: 491–504. doi: 10.1189/jlb.1208728 19401387

48. Forestal CA, Malik M, Catlett SV, Savitt AG, Benach JL, et al. (2007) Francisella tularensis has a significant extracellular phase in infected mice. J Infect Dis 196: 134–137. 17538893

49. Chiavolini D, Alroy J, King CA, Jorth P, Weir S, et al. (2008) Identification of immunologic and pathologic parameters of death versus survival in respiratory tularemia. Infect Immun 76: 486–496. 18025095

50. Furuya Y, Kirimanjeswara GS, Roberts S, Metzger DW (2013) Increased susceptibility of IgA-deficient mice to pulmonary Francisella tularensis Live Vaccine Strain infection. Infect Immun 81: 3434–3441. doi: 10.1128/IAI.00408-13 23836815

51. Foo SY, Phipps S (2010) Regulation of inducible BALT formation and contribution to immunity and pathology. Mucosal Immunol 3: 537–544. doi: 10.1038/mi.2010.52 20811344

52. Melillo AA, Foreman O, Elkins KL (2013) IL-12Rbeta2 is critical for survival of primary Francisella tularensis LVS infection. J Leukoc Biol 93: 657–667. doi: 10.1189/jlb.1012485 23440500

53. Notas G, Kisseleva T, Brenner D (2009) NK and NKT cells in liver injury and fibrosis. Clin Immunol 130: 16–26. doi: 10.1016/j.clim.2008.08.008 18823822

54. Gao B, Radaeva S, Park O (2009) Liver natural killer and natural killer T cells: immunobiology and emerging roles in liver diseases. J Leukoc Biol 86: 513–528. doi: 10.1189/JLB.0309135 19542050

55. von Vietinghoff S, Ley K (2008) Homeostatic regulation of blood neutrophil counts. J Immunol 181: 5183–5188. 18832668

56. Wu Z, Han M, Chen T, Yan W, Ning Q (2010) Acute liver failure: mechanisms of immune-mediated liver injury. Liver Int 30: 782–794. doi: 10.1111/j.1478-3231.2010.02262.x 20492514

57. Carnaud C, Lee D, Donnars O, Park SH, Beavis A, et al. (1999) Cutting edge: Cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. J Immunol 163: 4647–4650. 10528160

58. Bezbradica JS, Stanic AK, Matsuki N, Bour-Jordan H, Bluestone JA, et al. (2005) Distinct roles of dendritic cells and B cells in Va14Ja18 natural T cell activation in vivo. J Immunol 174: 4696–4705. 15814694

59. Kim JH, Oh SJ, Ahn S, Chung DH (2014) IFN-gamma-producing NKT cells exacerbate sepsis by enhancing C5a generation via IL-10-mediated inhibition of CD55 expression on neutrophils. Eur J Immunol 44: 2025–2035. doi: 10.1002/eji.201343937 24723363

60. Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, et al. (2012) Into the eye of the cytokine storm. Microbiol Mol Biol Rev 76: 16–32. doi: 10.1128/MMBR.05015-11 22390970

61. Chen W, Shen H, Webb A, KuoLee R, Conlan JW (2003) Tularemia in BALB/c and C57BL/6 mice vaccinated with Francisella tularensis LVS and challenged intradermally, or by aerosol with virulent isolates of the pathogen: protection varies depending on pathogen virulence, route of exposure, and host genetic background. Vaccine 21: 3690–3700. 12922099

62. Fortier AH, Slayter MV, Ziemba R, Meltzer MS, Nacy CA (1991) Live vaccine strain of Francisella tularensis: infection and immunity in mice. Infect Immun 59: 2922–2928. 1879918

63. Anthony LS, Skamene E, Kongshavn PA (1988) Influence of genetic background on host resistance to experimental murine tularemia. Infect Immun 56: 2089–2093. 3397185

64. Lopez MC, Duckett NS, Baron SD, Metzger DW (2004) Early activation of NK cells after lung infection with the intracellular bacterium, Francisella tularensis LVS. Cell Immunol 232: 75–85. 15922718

65. Anthony LS, Kongshavn PA (1987) Experimental murine tularemia caused by Francisella tularensis, live vaccine strain: a model of acquired cellular resistance. Microb Pathog 2: 3–14. 3507552

66. Duckett NS, Olmos S, Durrant DM, Metzger DW (2005) Intranasal interleukin-12 treatment for protection against respiratory infection with the Francisella tularensis live vaccine strain. Infect Immun 73: 2306–2311. 15784575

67. Kirimanjeswara GS, Golden JM, Bakshi CS, Metzger DW (2007) Prophylactic and therapeutic use of antibodies for protection against respiratory infection with Francisella tularensis. J Immunol 179: 532–539. 17579074

68. Henry T, Kirimanjeswara GS, Ruby T, Jones JW, Peng K, et al. (2010) Type I IFN signaling constrains IL-17A/F secretion by gammadelta T cells during bacterial infections. J Immunol 184: 3755–3767. doi: 10.4049/jimmunol.0902065 20176744

69. Rivas FV, Chervonsky AV, Medzhitov R (2014) ART and immunology. Trends Immunol 35: 451. doi: 10.1016/j.it.2014.09.002 25261059

70. Forestal CA, Benach JL, Carbonara C, Italo JK, Lisinski TJ, et al. (2003) Francisella tularensis selectively induces proinflammatory changes in endothelial cells. J Immunol 171: 2563–2570. 12928407

71. Moreland JG, Hook JS, Bailey G, Ulland T, Nauseef WM (2009) Francisella tularensis directly interacts with the endothelium and recruits neutrophils with a blunted inflammatory phenotype. Am J Physiol Lung Cell Mol Physiol 296: L1076–1084. doi: 10.1152/ajplung.90332.2008 19346432

72. Allen LA (2013) Neutrophils: potential therapeutic targets in tularemia? Front Cell Infect Microbiol 3: 109. doi: 10.3389/fcimb.2013.00109 24409419

73. Mocsai A (2013) Diverse novel functions of neutrophils in immunity, inflammation, and beyond. J Exp Med 210: 1283–1299. doi: 10.1084/jem.20122220 23825232

74. De Santo C, Arscott R, Booth S, Karydis I, Jones M, et al. (2010) Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A. Nat Immunol 11: 1039–1046. doi: 10.1038/ni.1942 20890286

75. Kotsianidis I, Silk JD, Spanoudakis E, Patterson S, Almeida A, et al. (2006) Regulation of hematopoiesis in vitro and in vivo by invariant NKT cells. Blood 107: 3138–3144. 16373666

76. Chiavolini D, Rangel-Moreno J, Berg G, Christian K, Oliveira-Nascimento L, et al. (2010) Bronchus-associated lymphoid tissue (BALT) and survival in a vaccine mouse model of tularemia. PLoS One 5: e11156. doi: 10.1371/journal.pone.0011156 20585390

77. Wayne Conlan J, Shen H, Kuolee R, Zhao X, Chen W (2005) Aerosol-, but not intradermal-immunization with the live vaccine strain of Francisella tularensis protects mice against subsequent aerosol challenge with a highly virulent type A strain of the pathogen by an alphabeta T cell- and interferon gamma- dependent mechanism. Vaccine 23: 2477–2485. 15752834

78. Elliot JG, Jensen CM, Mutavdzic S, Lamb JP, Carroll NG, et al. (2004) Aggregations of lymphoid cells in the airways of nonsmokers, smokers, and subjects with asthma. Am J Respir Crit Care Med 169: 712–718. 14711796

79. Bezbradica JS, Stanic AK, Joyce S (2006) Characterization and functional analysis of mouse invariant natural T (iNKT) cells. Curr Protoc Immunol Chapter 14: Unit 14 13.

80. Misharin AV, Morales-Nebreda L, Mutlu GM, Budinger GR, Perlman H (2013) Flow cytometric analysis of macrophages and dendritic cell subsets in the mouse lung. Am J Respir Cell Mol Biol 49: 503–510. doi: 10.1165/rcmb.2013-0086MA 23672262

81. Freedman DA (2006) On the so-called “Huber sandwich estimator” and “robust standard errors”.. American Statistician 60: 299–302.

82. Huber PJ (1967) The behavior of maximum likelihood estimates under nonstandard conditions.. Proceedings of the Fifth Berkeley Symposium on Mathematical Statistics and Probability: 221–233.

83. White H (1980) A Heteroskedasticity-Consistent Covariance Matrix Estimator and a Direct Test for Heteroskedasticity. Econometrica 48: 817–838.

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2015 Číslo 6
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#