Squalene emulsion potentiates the adjuvant activity of the TLR4 agonist, GLA, via inflammatory caspases, IL-18, and IFN-γ

European Journal of Immunology

Volumn 45, Issue 2, 2015, Pages 407-417

  Desbien, Anthony L ^a   Reed, Steven J ^a   Bailor, Hilton R ^a   Cauwelaert, Natasha Dubois ^a   Laurance, John D ^a   Orr, Mark T ^a   Fox, Christopher B ^a   Carter, Darrick ^a,b   Reed, Steven G ^a   Duthie, Malcolm S ^a  

^a INFECTIOUS DISEASE RESEARCH INSTITUTE   (United States)

^b PAI Life Sciences   (United States)

Author keywords

Adjuvants; Innate immunity; Squalene; Th1 immunity; TLR4

Indexed keywords

CASPASE; CASPASE 11; GAMMA INTERFERON; GLUCOPYRANOSYL LIPID ADJUVANT; IMMUNOLOGICAL ADJUVANT; INFLAMMASOME; INTERLEUKIN 18; INTERLEUKIN 1BETA CONVERTING ENZYME; SQUALENE; TOLL LIKE RECEPTOR AGONIST; UNCLASSIFIED DRUG; WATER OIL CREAM; CASP11 PROTEIN, MOUSE; EMULSION; INTERLEUKIN 18 RECEPTOR; LIPID; TLR4 PROTEIN, MOUSE; TOLL LIKE RECEPTOR 4;

ADAPTIVE IMMUNITY; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DRUG EFFECT; DRUG FORMULATION; DRUG MECHANISM; EMULSION; FEMALE; IMMUNOFLUORESCENCE MICROSCOPY; IMMUNOHISTOLOGY; INNATE IMMUNITY; INTRAPLANTAR DRUG ADMINISTRATION; MEMORY T LYMPHOCYTE; MOUSE; NEUTROPHIL; NONHUMAN; PRIORITY JOURNAL; TH1 CELL; AGONISTS; ANIMAL; BIOSYNTHESIS; CHEMISTRY; CYTOLOGY; DRUG EFFECTS; GENE EXPRESSION; GENETICS; IMMUNIZATION; IMMUNOLOGICAL MEMORY; IMMUNOLOGY; KNOCKOUT MOUSE; SYNTHESIS;

ADAPTIVE IMMUNITY; ADJUVANTS, IMMUNOLOGIC; ANIMALS; CASPASE 1; CASPASES; CD8-POSITIVE T-LYMPHOCYTES; EMULSIONS; FEMALE; GENE EXPRESSION; IMMUNITY, INNATE; IMMUNIZATION; IMMUNOLOGIC MEMORY; INFLAMMASOMES; INTERFERON-GAMMA; INTERLEUKIN-18; LIPIDS; MICE; MICE, KNOCKOUT; NEUTROPHILS; RECEPTORS, INTERLEUKIN-18; SQUALENE; TH1 CELLS; TOLL-LIKE RECEPTOR 4;

EID: 84923040359     PISSN: 00142980     EISSN: 15214141     Source Type: Journal    
DOI: 10.1002/eji.201444543     Document Type: Article

References (63)

1. McKee, A. S., Munks, M. W. and Marrack, P., How do adjuvants work? Important considerations for new generation adjuvants. Immunity 2007. 27: 687-690.
2. Marrack, P., McKee, A. and Munks, M., Towards an understanding of the adjuvant action of aluminium. Nat. Rev. Immunol. 2009. 9: 287-293.
3. O'Hagan, D. T., Ott, G. S., De Gregorio, E. and Seubert, A., The mechanism of action of MF59-an innately attractive adjuvant formulation. Vaccine 2012. 30: 4341-4348.
4. Carter, D. and Reed, S. G., Role of adjuvants in modeling the immune response. Curr. Opin. HIV AIDS 2010. 5: 409-413.
5. Coler, R. N., Baldwin, S. L., Shaverdian, N., Bertholet, S., Reed, S. J., Raman, V. S., Lu, X. et al., A synthetic adjuvant to enhance and expand immune responses to influenza vaccines. PLoS One 2010. 5: e13677.
6. Stoute, J. A., Slaoui, M., Heppner, D. G., Momin, P., Kester, K. E., Desmons, P., Wellde, B. T. et al., A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. RTS, S Malaria Vaccine Evaluation Group. N. Engl. J. Med. 1997. 336: 86-91.
7. Baudner, B. C., Ronconi, V., Casini, D., Tortoli, M., Kazzaz, J., Singh, M., Hawkins, L. D. et al., MF59 emulsion is an effective delivery system for a synthetic TLR4 agonist (E6020). Pharm. Res. 2009. 26: 1477-1485.
8. Anderson, R. C., Fox, C. B., Dutill, T. S., Shaverdian, N., Evers, T. L., Poshusta, G. R., Chesko, J. et al., Physicochemical characterization and biological activity of synthetic TLR4 agonist formulations. Colloids Surf. B. Biointerfaces. 2010. 75: 123-132.
9. Lousada-Dietrich, S., Jogdand, P. S., Jepsen, S., Pinto, V. V., Ditlev, S. B., Christiansen, M., Larsen, S. O. et al., A synthetic TLR4 agonist formulated in an emulsion enhances humoral and Type 1 cellular immune responses against GMZ2-a GLURP-MSP3 fusion protein malaria vaccine candidate. Vaccine 2011. 29: 3284-3292.
10. Coler, R. N., Bertholet, S., Pine, S. O., Orr, M. T., Reese, V., Windish, H. P., Davis, C. et al., Therapeutic immunization against Mycobacterium tuberculosis is an effective adjunct to antibiotic treatment. J. Infect. Dis. 2013. 207: 1242-1252.
11. Bertholet, S., Ireton, G. C., Ordway, D. J., Windish, H. P., Pine, S. O., Kahn, M., Phan, T. et al., A defined tuberculosis vaccine candidate boosts BCG and protects against multidrug-resistant Mycobacterium tuberculosis. Sci. Transl. Med. 2010. 2: 53ra74.
12. Mosca, F., Tritto, E., Muzzi, A., Monaci, E., Bagnoli, F., Iavarone, C., O'Hagan, D. et al., Molecular and cellular signatures of human vaccine adjuvants. Proc. Natl. Acad. Sci. USA 2008. 105: 10501-10506.
13. Seubert, A., Monaci, E., Pizza, M., O'Hagan, D. T., and Wack, A., The adjuvants aluminum hydroxide and MF59 induce monocyte and granulocyte chemoattractants and enhance monocyte differentiation toward dendritic cells. J. Immunol. 2008. 180: 5402-5412.
14. Morel, S., Didierlaurent, A., Bourguignon, P., Delhaye, S., Baras, B., Jacob, V., Planty, C. et al., Adjuvant System AS03 containing α-tocopherol modulates innate immune response and leads to improved adaptive immunity. Vaccine 2011. 29: 2461-2473.
15. Davis, B. K., Wen, H. and Ting, J. P.-Y., The inflammasome NLRs in immunity, inflammation, and associated diseases. Annu. Rev. Immunol. 2011. 29: 707-735.
16. Bryant, C. and Fitzgerald, K. A., Molecular mechanisms involved in inflammasome activation. Trends Cell Biol. 2009. 19: 455-464.
17. Vono, M., Taccone, M., Caccin, P., Gallotta, M., Donvito, G., Falzoni, S., Palmieri, E. et al., The adjuvant MF59 induces ATP release from muscle that potentiates response to vaccination. Proc. Natl. Acad. Sci. USA 2013. 110: 21095-21100.
18. Ellebedy, A. H., Lupfer, C., Ghoneim, H. E., DeBeauchamp, J., Kanneganti, T.-D. and Webby, R. J., Inflammasome-independent role of the apoptosis-associated speck-like protein containing CARD (ASC) in the adjuvant effect of MF59. Proc. Natl. Acad. Sci. USA 2011. 108: 2927-2932.
19. Takeda, K., Tsutsui, H., Yoshimoto, T., Adachi, O., Yoshida, N., Kishimoto, T., Okamura, H. et al., Defective NK cell activity and Th1 response in IL-18-deficient mice. Immunity 1998. 8: 383-390.
20. Nguyen, K. B. and Biron, C. A., Synergism for cytokine-mediated disease during concurrent endotoxin and viral challenges: roles for NK and T cell IFN-gamma production. J. Immunol. 1999. 162: 5238-5246.
21. Berg, R. E., Crossley, E., Murray, S. and Forman, J., Memory CD8+ T cells provide innate immune protection against Listeria monocytogenes in the absence of cognate antigen. J. Exp. Med. 2003. 198: 1583-1593.
22. Mencacci, A., Bacci, A., Cenci, E., Montagnoli, C., Fiorucci, S., Casagrande, A., Flavell, R. A. et al., Interleukin 18 restores defective Th1 immunity to Candida albicans in caspase 1-deficient mice. Infect. Immun. 2000. 68: 5126-5131.
23. Maxwell, J. R., Yadav, R., Rossi, R. J., Ruby, C. E., Weinberg, A. D., Aguila, H. L. and Vella, A. T., IL-18 bridges innate and adaptive immunity through IFN-gamma and the CD134 pathway. J. Immunol. 2006. 177: 234-245.
24. Orr, M. T., Fox, C. B., Baldwin, S. L., Sivananthan, S. J., Lucas, E., Lin, S., Phan, T. et al., Adjuvant formulation structure and composition is critical for the development of an effective vaccine against tuberculosis. J. Control. Release 2013. 172: 190-200.
25. Windish, H. P., Duthie, M. S., Misquith, A., Ireton, G., Lucas, E., Laurance, J. D., Bailor, R. H. et al., Protection of mice from Mycobacterium tuberculosis by ID87/GLA-SE, a novel tuberculosis subunit vaccine candidate. Vaccine 2011. 29: 7842-7848.
26. Sun, S., Zhang, X., Tough, D. F. and Sprent, J., Type I interferon-mediated stimulation of T cells by CpG DNA. J. Exp. Med. 1998. 188: 2335-2342.
27. Matloubian, M., Lo, C. G., Cinamon, G., Lesneski, M. J., Xu, Y., Brinkmann, V., Allende, M. L. et al., Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 2004. 427: 355-360.
28. Shiow, L. R., Rosen, D. B., Brdicková, N., Xu, Y., An, J., Lanier, L. L., Cyster, J. G. et al., CD69 acts downstream of interferon-alpha/beta to inhibit S1P1 and lymphocyte egress from lymphoid organs. Nature 2006. 440: 540-544.
29. Qiao, Y., Giannopoulou, E. G., Chan, C. H., Park, S.-H., Gong, S., Chen, J., Hu, X. et al., Synergistic activation of inflammatory cytokine genes by interferon-γ-induced chromatin remodeling and Toll-like receptor signaling. Immunity 2013. 39: 454-469.
30. Bradley, L. M., Dalton, D. K. and Croft, M., A direct role for IFN-gamma in regulation of Th1 cell development. J. Imunol. 1996. 157: 1350-1358.
31. Lighvani, A. A., Frucht, D. M., Jankovic, D., Yamane, H., Aliberti, J., Hissong, B. D., Nguyen, B. V. et al., T-bet is rapidly induced by interferon-gamma in lymphoid and myeloid cells. Proc. Natl. Acad. Sci. USA 2001. 98: 15137-15142.
32. Martín-Fontecha, A., Thomsen, L. L., Brett, S., Gerard, C., Lipp, M., Lanzavecchia, A. and Sallusto, F., Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1 priming. Nat. Immunol. 2004. 5: 1260-1265.
33. Choi, Y. S., Kageyama, R., Eto, D., Escobar, T. C., Johnston, R. J., Monticelli, L., Lao, C. et al., ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6. Immunity 2011. 34: 932-946.
34. Pepper, M., Pagán, A. J., Igyártó, B. Z., Taylor, J. J. and Jenkins, M. K., Opposing signals from the Bcl6 transcription factor and the interleukin-2 receptor generate T helper 1 central and effector memory cells. Immunity 2011. 35: 583-595.
35. Eisenbarth, S. C., Colegio, O. R., O'Connor, W., Sutterwala, F. S. and Flavell, R. A., Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature 2008. 453: 1122-1126.
36. McKee, A. S., Munks, M. W., MacLeod, M. K. L., Fleenor, C. J., Van Rooijen, N., Kappler, J. W. and Marrack, P., Alum induces innate immune responses through macrophage and mast cell sensors, but these sensors are not required for alum to act as an adjuvant for specific immunity. J. Imunol. 2009. 183: 4403-4414.
37. Mitchell, A. J., Yau, B., McQuillan, J. A., Ball, H. J., Too, L. K., Abtin, A., Hertzog, P. et al., Inflammasome-dependent IFN-γ drives pathogenesis in Streptococcus pneumoniae meningitis. J. Immunol. 2012. 189: 4970-4980.
38. Kastenmüller, W., Torabi-Parizi, P., Subramanian, N., Lämmermann, T. and Germain, R. N., A spatially-organized multicellular innate immune response in lymph nodes limits systemic pathogen spread. Cell 2012. 150: 1235-1248.
39. Oghumu, S., Dong, R., Varikuti, S., Shawler, T., Kampfrath, T., Terrazas, C. A., Lezama-Davila, C. et al., Distinct populations of innate CD8+ T cells revealed in a CXCR3 reporter mouse. J. Immunol. 2013. 190: 2229-2240.
40. Ng, T. M., Monack, D. M., Revisiting caspase-11 function in host defense. Cell Host Microbe 2013. 14: 9-14.
41. Calabro, S., Tortoli, M., Baudner, B. C., Pacitto, A., Cortese, M., O'Hagan, D. T., De Gregorio, E. et al., Vaccine adjuvants alum and MF59 induce rapid recruitment of neutrophils and monocytes that participate in antigen transport to draining lymph nodes. Vaccine 2011. 29: 1812-1823.
42. Mogensen, T. H., Pathogen recognition and inflammatory signaling in innate immune defenses. Clin. Microbiol. Rev. 2009. 22: 240-273.
43. Kasturi, S. P., Skountzou, I., Albrecht, R. A., Koutsonanos, D., Hua, T., Nakaya, H. I., Ravindran, R. et al., Programming the magnitude and persistence of antibody responses with innate immunity. Nature 2011. 470: 543-547.
44. Soltysik, S., Wu, J. Y., Recchia, J., Wheeler, D. A., Newman, M. J., Coughlin, R. T. and Kensil, C. R., Structure/function studies of QS-21 adjuvant: assessment of triterpene aldehyde and glucuronic acid roles in adjuvant function. Vaccine 1995. 13: 1403-1410.
45. Seubert, A., Calabro, S., Santini, L., Galli, B., Genovese, A., Valentini, S., Aprea, S. et al., Adjuvanticity of the oil-in-water emulsion MF59 is independent of Nlrp3 inflammasome but requires the adaptor protein MyD88. Proc. Natl. Acad. Sci. USA 2011. 108: 11169-11174.
46. Ashtekar, A. R. and Saha, B., Poly's plea: membership to the club of APCs. Trends Immunol. 2003. 24: 485-490.
47. Beauvillain, C., Delneste, Y., Scotet, M., Peres, A., Gascan, H., Guermonprez, P., Barnaba, V. et al., Neutrophils efficiently cross-prime naive T cells in vivo. Blood 2007. 110: 2965-2973.
48. Wright, H. L., Moots, R. J., Bucknall, R. C., and Edwards, S. W., Neutrophil function in inflammation and inflammatory diseases. Rheumatology 2010. 49: 1618-1631.
49. Yang, C., Strong, B. S. I., Miller, M. J. and Unanue, E. R., Neutrophils influence the level of antigen presentation during the immune response to protein antigens in adjuvants. J. Immunol. 2010. 185: 2927-2934.
50. Mocsai, A., Diverse novel functions of neutrophils in immunity, inflammation, and beyond. J. Exp. Med. 2013. 210: 1283-1299.
51. Sturge, C. R., Benson, A., Raetz, M., Wilhelm, C. L., Mirpuri, J., Vitetta, E. S. and Yarovinsky, F., TLR-independent neutrophil-derived IFN-γ is important for host resistance to intracellular pathogens. Proc. Natl. Acad. Sci. USA 2013. 110: 10711-10716.
52. Puga, I., Cols, M., Barra, C. M., He, B., Cassis, L., Gentile, M., Comerma, L. et al., B cell-helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen. Nat. Immunol. 2012. 13: 170-180.
53. Groom, J. R., Richmond, J., Murooka, T. T., Sorensen, E. W., Sung, J. H., Bankert, K., von Andrian, U. H. et al., CXCR3 chemokine receptor-ligand interactions in the lymph node optimize CD4+ T helper 1 cell differentiation. Immunity 2012. 37: 1091-1103.
54. Wakil, A. E., Wang, Z. E., Ryan, J. C., Fowell, D. J. and Locksley, R. M., Interferon gamma derived from CD4(+) T cells is sufficient to mediate T helper cell type 1 development. J. Exp. Med. 1998. 188: 1651-1656.
55. Longhi, M. P., Trumpfheller, C., Idoyaga, J., Caskey, M., Matos, I., Kluger, C., Salazar, A. M. et al., Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J. Exp. Med. 2009. 206: 1589-1602.
56. Daley, J. M., Thomay, A. A., Connolly, M. D., Reichner, J. S. and Albina, J. E., Use of Ly6G-specific monoclonal antibody to deplete neutrophils in mice. J. Leukoc. Biol. 2008. 83: 64-70.
57. Shi, J., Zhao, Y., Wang, Y., Gao, W., Ding, J., Li, P., Hu, L. et al., Inflammatory caspases are innate immune receptors for intracellular LPS. Nature 2014. 514: 187-192.
58. Hagar, J. A., Powell, D. A., Aachoui, Y., Ernst, R. K. and Miao, E. A., Cytoplasmic LPS activates caspase-11: implications in TLR4-independent endotoxic shock. Science 2013. 341: 1250-1253.
59. Kayagaki, N., Wong, M. and Stowe, I., Noncanonical inflammasome activation by intracellular LPS independent of TLR4. Science 2013. 1246: 1246-1249.
60. Kayagaki, N., Warming, S., Lamkanfi, M., Vande Walle, L., Louie, S., Dong, J., Newton, K. et al., Non-canonical inflammasome activation targets caspase-11. Nature 2011. 479: 117-121.
61. Misquith, A., Fung, H. W. M., Dowling, Q. M., Guderian, J. A., Vedvick, T. S. and Fox, C. B., In vitro evaluation of TLR4 agonist activity: formulation effects. Colloids Surf. B 2014. 113: 312-319.
62. Roederer, M., Nozzi, J. L. and Nason, M. C., SPICE: exploration and analysis of post-cytometric complex multivariate datasets. Cytometry A 2011. 79: 167-174.
63. Schneider, C. A., Rasband, W. S. and Eliceiri, K. W., NIH Image to ImageJ: 25 years of image analysis. Nat. Methods 2012. 9: 671-675.