Skip to main content
SpringerLink
Log in

The role of invariant natural killer T cells in microbial immunity

  • Review Article
  • Published:
Journal of Infection and Chemotherapy

Abstract

Invariant natural killer T cells (iNKT cells) are unique lymphocytes with characteristic features, such as expression of an invariant T-cell antigen receptor (TCR) α-chain, recognition of glycolipid antigens presented by CD1d molecules, and ability to rapidly produce large amounts of cytokines, including interferon-γ (IFN-γ) and interleukin 4 (IL-4) upon TCR stimulation. Many studies have demonstrated that iNKT cells participate in immune response against diverse microbes, including bacteria, fungi, protozoan parasites, and viruses. Generally, these cells play protective roles in host defense against infections. However, in some contexts they play pathogenic roles, by inducing or augmenting inflammation. Recent reports show that iNKT cells recognize glycolipid antigens from pathogenic bacteria including Streptococcus pneumoniae, and they contribute to host defense against infection. iNKT cell responses to these microbial glycolipid antigens are highly conserved between rodents and humans, suggesting that iNKT cells are evolutionally conserved because their invariant TCR is useful in detecting certain pathogens. Furthermore, glycolipid-mediated iNKT cell activation during immunization has adjuvant activity, enhancing humoral and cell-mediated responses. Therefore, iNKT cell activation is an attractive target for developing new vaccines for infectious diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Tupin E, Kinjo Y, Kronenberg M. The unique role of natural killer T cells in the response to microorganisms. Nat Rev Microbiol. 2007;5:405–17.

    Article  PubMed  CAS  Google Scholar 

  2. Taniguchi M, Tashiro T, Dashtsoodol N, Hongo N, Watarai H. The specialized iNKT cell system recognizes glycolipid antigens and bridges the innate and acquired immune systems with potential applications for cancer therapy. Int Immunol. 2010;22:1–6.

    Article  PubMed  CAS  Google Scholar 

  3. Brigl M, Brenner MB. How invariant natural killer T cells respond to infection by recognizing microbial or endogenous lipid antigens. Semin Immunol. 2010;22:79–86.

    Article  PubMed  CAS  Google Scholar 

  4. Pei B, Vela JL, Zajonc D, Kronenberg M. Interplay between carbohydrate and lipid in recognition of glycolipid antigens by natural killer T cells. Ann N Y Acad Sci. 2012;1253:68–79.

    Article  PubMed  CAS  Google Scholar 

  5. Rossjohn J, Pellicci DG, Patel O, Gapin L, Godfrey DI. Recognition of CD1d-restricted antigens by natural killer T cells. Nat Rev Immunol. 2012;12:845–57.

    Article  PubMed  CAS  Google Scholar 

  6. Zajonc DM, Kronenberg M. Carbohydrate specificity of the recognition of diverse glycolipids by natural killer T cells. Immunol Rev. 2009;230:188–200.

    Article  PubMed  CAS  Google Scholar 

  7. Godfrey DI, MacDonald HR, Kronenberg M, Smyth MJ, Van Kaer L. NKT cells: what’s in a name? Nat Rev Immunol. 2004;4:231–7.

    Article  PubMed  CAS  Google Scholar 

  8. Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y, Motoki K, et al. CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides. Science. 1997;278:1626–9.

    Article  PubMed  CAS  Google Scholar 

  9. Brossay L, Chioda M, Burdin N, Koezuka Y, Casorati G, Dellabona P, et al. CD1d-mediated recognition of an alpha-galactosylceramide by natural killer T cells is highly conserved through mammalian evolution. J Exp Med. 1998;188:1521–8.

    Article  PubMed  CAS  Google Scholar 

  10. Jahng A, Maricic I, Aguilera C, Cardell S, Halder RC, Kumar V. Prevention of autoimmunity by targeting a distinct, noninvariant CD1d-reactive T cell population reactive to sulfatide. J Exp Med. 2004;199:947–57.

    Article  PubMed  CAS  Google Scholar 

  11. Terabe M, Swann J, Ambrosino E, Sinha P, Takaku S, Hayakawa Y, et al. A nonclassical non-V alpha14J alpha18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance. J Exp Med. 2005;202:1627–33.

    Article  PubMed  CAS  Google Scholar 

  12. Rhost S, Lofbom L, Rynmark BM, Pei B, Mansson JE, Teneberg S, et al. Identification of novel glycolipid ligands activating a sulfatide-reactive, CD1d-restricted, type II natural killer T lymphocyte. Eur J Immunol. 2012;42:2851–60.

    Article  PubMed  CAS  Google Scholar 

  13. Tatituri RV, Watts GF, Bhowruth V, Barton N, Rothchild A, Hsu FF, et al. Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs. Proc Natl Acad Sci USA. 2013;110:1827–32.

    Article  PubMed  CAS  Google Scholar 

  14. Cui J, Shin T, Kawano T, Sato H, Kondo E, Toura I, et al. Requirement for Valpha14 NKT cells in IL-12-mediated rejection of tumors. Science. 1997;278:1623–6.

    Article  PubMed  CAS  Google Scholar 

  15. Kawakami K, Yamamoto N, Kinjo Y, Miyagi K, Nakasone C, Uezu K, et al. Critical role of Valpha14+ natural killer T cells in the innate phase of host protection against Streptococcus pneumoniae infection. Eur J Immunol. 2003;33:3322–30.

    Article  PubMed  CAS  Google Scholar 

  16. Nakamatsu M, Yamamoto N, Hatta M, Nakasone C, Kinjo T, Miyagi K, et al. Role of interferon-gamma in Valpha14+ natural killer T cell-mediated host defense against Streptococcus pneumoniae infection in murine lungs. Microbes Infect. 2007;9:364–74.

    Article  PubMed  CAS  Google Scholar 

  17. Bedel R, Matsuda JL, Brigl M, White J, Kappler J, Marrack P, et al. Lower TCR repertoire diversity in Traj18-deficient mice. Nat Immunol. 2012;13:705–6.

    Article  PubMed  CAS  Google Scholar 

  18. Kinjo Y, Illarionov P, Vela JL, Pei B, Girardi E, Li X, et al. Invariant natural killer T cells recognize glycolipids from pathogenic gram-positive bacteria. Nat Immunol. 2011;12:966–74.

    Article  PubMed  CAS  Google Scholar 

  19. Joyee AG, Qiu H, Wang S, Fan Y, Bilenki L, Yang X. Distinct NKT cell subsets are induced by different Chlamydia species leading to differential adaptive immunity and host resistance to the infections. J Immunol. 2007;178:1048–58.

    PubMed  CAS  Google Scholar 

  20. Joyee AG, Uzonna J, Yang X. Invariant NKT cells preferentially modulate the function of CD8 alpha+ dendritic cell subset in inducing type 1 immunity against infection. J Immunol. 2010;184:2095–106.

    Article  PubMed  CAS  Google Scholar 

  21. Peng Y, Zhao L, Shekhar S, Liu L, Wang H, Chen Q, et al. The glycolipid exoantigen derived from Chlamydia muridarum activates invariant natural killer T cells. Cell Mol Immunol. 2012;9:361–6.

    Article  PubMed  CAS  Google Scholar 

  22. Jiang J, Karimi O, Ouburg S, Champion CI, Khurana A, Liu G, et al. Interruption of CXCL13–CXCR5 axis increases upper genital tract pathology and activation of NKT cells following chlamydial genital infection. PLoS ONE. 2012;7:e47487.

    Article  PubMed  CAS  Google Scholar 

  23. Kawana K, Quayle AJ, Ficarra M, Ibana JA, Shen L, Kawana Y, et al. CD1d degradation in Chlamydia trachomatis-infected epithelial cells is the result of both cellular and chlamydial proteasomal activity. J Biol Chem. 2007;282:7368–75.

    Article  PubMed  CAS  Google Scholar 

  24. Wong CH, Jenne CN, Lee WY, Leger C, Kubes P. Functional innervation of hepatic iNKT cells is immunosuppressive following stroke. Science. 2011;334:101–5.

    Article  PubMed  CAS  Google Scholar 

  25. Kawakami K, Kinjo Y, Uezu K, Yara S, Miyagi K, Koguchi Y, et al. Monocyte chemoattractant protein-1-dependent increase of V alpha 14 NKT cells in lungs and their roles in Th1 response and host defense in cryptococcal infection. J Immunol. 2001;167:6525–32.

    PubMed  CAS  Google Scholar 

  26. Cohen NR, Tatituri RV, Rivera A, Watts GF, Kim EY, Chiba A, et al. Innate recognition of cell wall beta-glucans drives invariant natural killer T cell responses against fungi. Cell Host Microbe. 2011;10:437–50.

    Article  PubMed  CAS  Google Scholar 

  27. Ishikawa H, Hisaeda H, Taniguchi M, Nakayama T, Sakai T, Maekawa Y, et al. CD4(+) v(alpha)14 NKT cells play a crucial role in an early stage of protective immunity against infection with Leishmania major. Int Immunol. 2000;12:1267–74.

    Article  PubMed  CAS  Google Scholar 

  28. Mattner J, Donhauser N, Werner-Felmayer G, Bogdan C. NKT cells mediate organ-specific resistance against Leishmania major infection. Microbes Infect. 2006;8:354–62.

    Article  PubMed  CAS  Google Scholar 

  29. Amprey JL, Im JS, Turco SJ, Murray HW, Illarionov PA, Besra GS, et al. A subset of liver NK T cells is activated during Leishmania donovani infection by CD1d-bound lipophosphoglycan. J Exp Med. 2004;200:895–904.

    Article  PubMed  CAS  Google Scholar 

  30. Duthie MS, Kahn M, White M, Kapur RP, Kahn SJ. Critical proinflammatory and anti-inflammatory functions of different subsets of CD1d-restricted natural killer T cells during Trypanosoma cruzi infection. Infect Immun. 2005;73:181–92.

    Article  PubMed  CAS  Google Scholar 

  31. Tyznik AJ, Tupin E, Nagarajan NA, Her MJ, Benedict CA, Kronenberg M. Cutting edge: the mechanism of invariant NKT cell responses to viral danger signals. J Immunol. 2008;181:4452–6.

    PubMed  CAS  Google Scholar 

  32. Wesley JD, Tessmer MS, Chaukos D, Brossay L. NK cell-like behavior of Valpha14i NK T cells during MCMV infection. PLoS Pathog. 2008;4:e1000106.

    Article  PubMed  Google Scholar 

  33. Lee SH, Girard S, Macina D, Busa M, Zafer A, Belouchi A, et al. Susceptibility to mouse cytomegalovirus is associated with deletion of an activating natural killer cell receptor of the C-type lectin superfamily. Nat Genet. 2001;28:42–5.

    PubMed  CAS  Google Scholar 

  34. Daniels KA, Devora G, Lai WC, O’Donnell CL, Bennett M, Welsh RM. Murine cytomegalovirus is regulated by a discrete subset of natural killer cells reactive with monoclonal antibody to Ly49H. J Exp Med. 2001;194:29–44.

    Article  PubMed  CAS  Google Scholar 

  35. Ashkar AA, Rosenthal KL. Interleukin-15 and natural killer and NKT cells play a critical role in innate protection against genital herpes simplex virus type 2 infection. J Virol. 2003;77:10168–71.

    Article  PubMed  CAS  Google Scholar 

  36. Grubor-Bauk B, Simmons A, Mayrhofer G, Speck PG. Impaired clearance of herpes simplex virus type 1 from mice lacking CD1d or NKT cells expressing the semivariant V alpha 14-J alpha 281 TCR. J Immunol. 2003;170:1430–4.

    PubMed  CAS  Google Scholar 

  37. Cornish AL, Keating R, Kyparissoudis K, Smyth MJ, Carbone FR, Godfrey DI. NKT cells are not critical for HSV-1 disease resolution. Immunol Cell Biol. 2006;84:13–9.

    Article  PubMed  CAS  Google Scholar 

  38. Nieuwenhuis EE, Matsumoto T, Exley M, Schleipman RA, Glickman J, Bailey DT, et al. CD1d-dependent macrophage-mediated clearance of Pseudomonas aeruginosa from lung. Nat Med. 2002;8:588–93.

    Article  PubMed  CAS  Google Scholar 

  39. Kinjo T, Nakamatsu M, Nakasone C, Yamamoto N, Kinjo Y, Miyagi K, et al. NKT cells play a limited role in the neutrophilic inflammatory responses and host defense to pulmonary infection with Pseudomonas aeruginosa. Microbes Infect. 2006;8:2679–85.

    Article  PubMed  CAS  Google Scholar 

  40. Mannoor MK, Weerasinghe A, Halder RC, Reza S, Morshed M, Ariyasinghe A, et al. Resistance to malarial infection is achieved by the cooperation of NK1.1(+) and NK1.1(−) subsets of intermediate TCR cells which are constituents of innate immunity. Cell Immunol. 2001;211:96–104.

    Article  PubMed  CAS  Google Scholar 

  41. Hansen DS, Siomos MA, Buckingham L, Scalzo AA, Schofield L. Regulation of murine cerebral malaria pathogenesis by CD1d-restricted NKT cells and the natural killer complex. Immunity. 2003;18:391–402.

    Article  PubMed  CAS  Google Scholar 

  42. Kee SJ, Kwon YS, Park YW, Cho YN, Lee SJ, Kim TJ, et al. Dysfunction of natural killer T cells in patients with active Mycobacterium tuberculosis infection. Infect Immun. 2012;80:2100–8.

    Article  PubMed  CAS  Google Scholar 

  43. Levy O, Orange JS, Hibberd P, Steinberg S, LaRussa P, Weinberg A, et al. Disseminated varicella infection due to the vaccine strain of varicella-zoster virus, in a patient with a novel deficiency in natural killer T cells. J Infect Dis. 2003;188:948–53.

    Article  PubMed  Google Scholar 

  44. Banovic T, Yanilla M, Simmons R, Robertson I, Schroder WA, Raffelt NC, et al. Disseminated varicella infection caused by varicella vaccine strain in a child with low invariant natural killer T cells and diminished CD1d expression. J Infect Dis. 2011;204:1893–901.

    Article  PubMed  CAS  Google Scholar 

  45. Pasquier B, Yin L, Fondaneche MC, Relouzat F, Bloch-Queyrat C, Lambert N, et al. Defective NKT cell development in mice and humans lacking the adapter SAP, the X-linked lymphoproliferative syndrome gene product. J Exp Med. 2005;201:695–701.

    Article  PubMed  CAS  Google Scholar 

  46. Nichols KE, Hom J, Gong SY, Ganguly A, Ma CS, Cannons JL, et al. Regulation of NKT cell development by SAP, the protein defective in XLP. Nat Med. 2005;11:340–5.

    Article  PubMed  CAS  Google Scholar 

  47. Rigaud S, Fondaneche MC, Lambert N, Pasquier B, Mateo V, Soulas P, et al. XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome. Nature (Lond). 2006;444:110–4.

    Article  CAS  Google Scholar 

  48. Yuan W, Dasgupta A, Cresswell P. Herpes simplex virus evades natural killer T cell recognition by suppressing CD1d recycling. Nat Immunol. 2006;7:835–42.

    Article  PubMed  CAS  Google Scholar 

  49. Rao P, Pham HT, Kulkarni A, Yang Y, Liu X, Knipe DM, et al. Herpes simplex virus 1 glycoprotein B and US3 collaborate to inhibit CD1d antigen presentation and NKT cell function. J Virol. 2011;85:8093–104.

    Article  PubMed  CAS  Google Scholar 

  50. Hage CA, Kohli LL, Cho S, Brutkiewicz RR, Twigg HL 3rd, Knox KS. Human immunodeficiency virus gp120 downregulates CD1d cell surface expression. Immunol Lett. 2005;98:131–5.

    Article  PubMed  CAS  Google Scholar 

  51. Chen N, McCarthy C, Drakesmith H, Li D, Cerundolo V, McMichael AJ, et al. HIV-1 down-regulates the expression of CD1d via Nef. Eur J Immunol. 2006;36:278–86.

    Article  PubMed  CAS  Google Scholar 

  52. Sanchez DJ, Gumperz JE, Ganem D. Regulation of CD1d expression and function by a herpesvirus infection. J Clin Invest. 2005;115:1369–78.

    PubMed  CAS  Google Scholar 

  53. Kim EY, Battaile JT, Patel AC, You Y, Agapov E, Grayson MH, et al. Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease. Nat Med. 2008;14:633–40.

    Article  PubMed  CAS  Google Scholar 

  54. Lappas CM, Day YJ, Marshall MA, Engelhard VH, Linden J. Adenosine A2A receptor activation reduces hepatic ischemia reperfusion injury by inhibiting CD1d-dependent NKT cell activation. J Exp Med. 2006;203:2639–48.

    Article  PubMed  CAS  Google Scholar 

  55. Selmi C, Balkwill DL, Invernizzi P, Ansari AA, Coppel RL, Podda M, et al. Patients with primary biliary cirrhosis react against a ubiquitous xenobiotic-metabolizing bacterium. Hepatology. 2003;38:1250–7.

    Article  PubMed  CAS  Google Scholar 

  56. Mattner J, Savage PB, Leung P, Oertelt SS, Wang V, Trivedi O, et al. Liver autoimmunity triggered by microbial activation of natural killer T cells. Cell Host Microbe. 2008;3:304–15.

    Article  PubMed  CAS  Google Scholar 

  57. Kita H, Naidenko OV, Kronenberg M, Ansari AA, Rogers P, He XS, et al. Quantitation and phenotypic analysis of natural killer T cells in primary biliary cirrhosis using a human CD1d tetramer. Gastroenterology. 2002;123:1031–43.

    Article  PubMed  CAS  Google Scholar 

  58. Park SH, Benlagha K, Lee D, Balish E, Bendelac A. Unaltered phenotype, tissue distribution and function of V alpha14(+) NKT cells in germ-free mice. Eur J Immunol. 2000;30:620–5.

    Article  PubMed  CAS  Google Scholar 

  59. Wingender G, Stepniak D, Krebs P, Lin L, McBride S, Wei B, et al. Intestinal microbes affect phenotypes and functions of invariant natural killer T cells in mice. Gastroenterology. 2012;143:418–28.

    Article  PubMed  CAS  Google Scholar 

  60. Olszak T, An D, Zeissig S, Vera MP, Richter J, Franke A, et al. Microbial exposure during early life has persistent effects on natural killer T cell function. Science. 2012;336:489–93.

    Article  PubMed  CAS  Google Scholar 

  61. Heller F, Fuss IJ, Nieuwenhuis EE, Blumberg RS, Strober W. Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells. Immunity. 2002;17:629–38.

    Article  PubMed  CAS  Google Scholar 

  62. Chang YJ, Kim HY, Albacker LA, Lee HH, Baumgarth N, Akira S, et al. Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity. J Clin Invest. 2011;121:57–69.

    Article  PubMed  CAS  Google Scholar 

  63. Brigl M, Bry L, Kent SC, Gumperz JE, Brenner MB. Mechanism of CD1d-restricted natural killer T cell activation during microbial infection. Nat Immunol. 2003;4:1230–7.

    Article  PubMed  CAS  Google Scholar 

  64. Nagarajan NA, Kronenberg M. Invariant NKT cells amplify the innate immune response to lipopolysaccharide. J Immunol. 2007;178:2706–13.

    PubMed  CAS  Google Scholar 

  65. Fischer K, Scotet E, Niemeyer M, Koebernick H, Zerrahn J, Maillet S, et al. Mycobacterial phosphatidylinositol mannoside is a natural antigen for CD1d-restricted T cells. Proc Natl Acad Sci USA. 2004;101:10685–90.

    Article  PubMed  CAS  Google Scholar 

  66. Kinjo Y, Wu D, Kim G, Xing GW, Poles MA, Ho DD, et al. Recognition of bacterial glycosphingolipids by natural killer T cells. Nature (Lond). 2005;434:520–5.

    Article  CAS  Google Scholar 

  67. Mattner J, Debord KL, Ismail N, Goff RD, Cantu C 3rd, Zhou D, et al. Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature (Lond). 2005;434:525–9.

    Article  CAS  Google Scholar 

  68. Sriram V, Du W, Gervay-Hague J, Brutkiewicz RR. Cell wall glycosphingolipids of Sphingomonas paucimobilis are CD1d-specific ligands for NKT cells. Eur J Immunol. 2005;35:1692–701.

    Article  PubMed  CAS  Google Scholar 

  69. Neef A, Witzenberger R, Kampfer P. Detection of sphingomonads and in situ identification in activated sludge using 16S rRNA-targeted oligonucleotide probes. J Ind Microbiol Biotechnol. 1999;23:261–7.

    Article  PubMed  CAS  Google Scholar 

  70. Long X, Deng S, Mattner J, Zang Z, Zhou D, McNary N, et al. Synthesis and evaluation of stimulatory properties of Sphingomonadaceae glycolipids. Nat Chem Biol. 2007;3:559–64.

    Article  PubMed  CAS  Google Scholar 

  71. Kinjo Y, Pei B, Bufali S, Raju R, Richardson SK, Imamura M, et al. Natural Sphingomonas glycolipids vary greatly in their ability to activate natural killer T cells. Chem Biol. 2008;15:654–64.

    Article  PubMed  CAS  Google Scholar 

  72. Brown LCW, Penaranda C, Kashyap PC, Williams BB, Clardy J, Kronenberg M, et al. Production of an NKT cell stimulatory glycosphingolipid by a prominent member of the human gut microbiota PLoS Biol 2013 (in press).

  73. Kinjo Y, Tupin E, Wu D, Fujio M, Garcia-Navarro R, Benhnia MR, et al. Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria. Nat Immunol. 2006;7:978–86.

    Article  PubMed  CAS  Google Scholar 

  74. Ben-Menachem G, Kubler-Kielb J, Coxon B, Yergey A, Schneerson R. A newly discovered cholesteryl galactoside from Borrelia burgdorferi. Proc Natl Acad Sci USA. 2003;100:7913–8.

    Article  PubMed  CAS  Google Scholar 

  75. O’Brien KL, Wolfson LJ, Watt JP, Henkle E, Deloria-Knoll M, McCall N, et al. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet. 2009;374:893–902.

    Article  PubMed  Google Scholar 

  76. Li Y, Girardi E, Wang J, Yu ED, Painter GF, Kronenberg M, et al. The Valpha14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode. J Exp Med. 2010;207:2383–93.

    Article  PubMed  CAS  Google Scholar 

  77. Girardi E, Yu ED, Li Y, Tarumoto N, Pei B, Wang J, et al. Unique interplay between sugar and lipid in determining the antigenic potency of bacterial antigens for NKT cells. PLoS Biol. 2011;9:e1001189.

    Article  PubMed  CAS  Google Scholar 

  78. Wu D, Zajonc DM, Fujio M, Sullivan BA, Kinjo Y, Kronenberg M, et al. Design of natural killer T cell activators: structure and function of a microbial glycosphingolipid bound to mouse CD1d. Proc Natl Acad Sci USA. 2006;103:3972–7.

    Article  PubMed  CAS  Google Scholar 

  79. Tupin E, Benhnia MR, Kinjo Y, Patsey R, Lena CJ, Haller MC, et al. NKT cells prevent chronic joint inflammation after infection with Borrelia burgdorferi. Proc Natl Acad Sci USA. 2008;105:19863–8.

    Article  PubMed  CAS  Google Scholar 

  80. Olson CM Jr, Bates TC, Izadi H, Radolf JD, Huber SA, Boyson JE, et al. Local production of IFN-gamma by invariant NKT cells modulates acute Lyme carditis. J Immunol. 2009;182:3728–34.

    Article  PubMed  CAS  Google Scholar 

  81. Lee WY, Moriarty TJ, Wong CH, Zhou H, Strieter RM, van Rooijen N, et al. An intravascular immune response to Borrelia burgdorferi involves Kupffer cells and iNKT cells. Nat Immunol. 2010;11:295–302.

    Article  PubMed  CAS  Google Scholar 

  82. Geissmann F, Cameron TO, Sidobre S, Manlongat N, Kronenberg M, Briskin MJ, et al. Intravascular immune surveillance by CXCR6+ NKT cells patrolling liver sinusoids. PLoS Biol. 2005;3:e113.

    Article  PubMed  Google Scholar 

  83. Brigl M, Tatituri RV, Watts GF, Bhowruth V, Leadbetter EA, Barton N, et al. Innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer T cell activation during microbial infection. J Exp Med. 2011;208:1163–77.

    Article  PubMed  CAS  Google Scholar 

  84. Ko SY, Ko HJ, Chang WS, Park SH, Kweon MN, Kang CY. Alpha-galactosylceramide can act as a nasal vaccine adjuvant inducing protective immune responses against viral infection and tumor. J Immunol. 2005;175:3309–17.

    PubMed  CAS  Google Scholar 

  85. Youn HJ, Ko SY, Lee KA, Ko HJ, Lee YS, Fujihashi K, et al. A single intranasal immunization with inactivated influenza virus and alpha-galactosylceramide induces long-term protective immunity without redirecting antigen to the central nervous system. Vaccine. 2007;25:5189–98.

    Article  PubMed  CAS  Google Scholar 

  86. Kamijuku H, Nagata Y, Jiang X, Ichinohe T, Tashiro T, Mori K, et al. Mechanism of NKT cell activation by intranasal coadministration of alpha-galactosylceramide, which can induce cross-protection against influenza viruses. Mucosal Immunol. 2008;1:208–18.

    Article  PubMed  CAS  Google Scholar 

  87. Guillonneau C, Mintern JD, Hubert FX, Hurt AC, Besra GS, Porcelli S, et al. Combined NKT cell activation and influenza virus vaccination boosts memory CTL generation and protective immunity. Proc Natl Acad Sci USA. 2009;106:3330–5.

    Article  PubMed  CAS  Google Scholar 

  88. Li X, Fujio M, Imamura M, Wu D, Vasan S, Wong CH, et al. Design of a potent CD1d-binding NKT cell ligand as a vaccine adjuvant. Proc Natl Acad Sci USA. 2010;107:13010–5.

    Article  PubMed  CAS  Google Scholar 

  89. Lindqvist M, Persson J, Thorn K, Harandi AM. The mucosal adjuvant effect of alpha-galactosylceramide for induction of protective immunity to sexually transmitted viral infection. J Immunol. 2009;182:6435–43.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the US National Institutes of Health grants (AI45053, AI69296, AI71922 to M.K.), the Japan Society for the Promotion of Science and Ministry of Education, Culture, Sports, Science and Technology (25713038), the Ministry of Health, Labor and Welfare of Japan (H25-shinkou-wakate-005), the Mochida Memorial Foundation for Medical and Pharmaceutical Research, Takeda Science Foundation, and Kato Memorial Bioscience Foundation (to Y.K.).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo, 162-8640, Japan

    Yuki Kinjo & Naoki Kitano

  2. Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA, 92037, USA

    Mitchell Kronenberg

Authors
  1. Yuki Kinjo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naoki Kitano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mitchell Kronenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mitchell Kronenberg.

About this article

Cite this article

Kinjo, Y., Kitano, N. & Kronenberg, M. The role of invariant natural killer T cells in microbial immunity. J Infect Chemother 19, 560–570 (2013). https://doi.org/10.1007/s10156-013-0638-1

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10156-013-0638-1

Keywords

Search

Navigation