B cell-intrinsic MyD88 signaling controls IFN-γ-mediated early IgG2c class switching in mice in response to a particulate adjuvant.
Adjuvants, Immunologic
/ pharmacology
Animals
B-Lymphocytes
/ immunology
Dendritic Cells
/ immunology
Immunoglobulin Class Switching
/ immunology
Immunoglobulin G
/ immunology
Interferon-gamma
/ immunology
Killer Cells, Natural
/ immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Differentiation Factor 88
/ immunology
Signal Transduction
/ immunology
T-Lymphocytes
/ immunology
B cells
IFN-γ
adjuvant
class switching
intrinsic MyD88
Journal
European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
04
01
2019
revised:
27
03
2019
accepted:
13
05
2019
pubmed:
16
5
2019
medline:
29
5
2020
entrez:
16
5
2019
Statut:
ppublish
Résumé
Adjuvants improve the potency of vaccines, but the modes of action (MOAs) of most adjuvants are largely unknown. TLR-dependent and -independent innate immune signaling through the adaptor molecule MyD88 has been shown to be pivotal to the effects of most adjuvants; however, MyD88's involvement in the TLR-independent MOAs of adjuvants is poorly understood. Here, using the T-dependent antigen NIPOVA and a unique particulate adjuvant called synthetic hemozoin (sHZ), we show that MyD88 is required for early GC formation and enhanced antibody class-switch recombination (CSR) in mice. Using cell-type-specific MyD88 KO mice, we found that IgG2c class switching, but not IgG1 class switching, was controlled by B cell-intrinsic MyD88 signaling. Notably, IFN-γ produced by various cells including T cells, NK cells, and dendritic cells was the primary cytokine for IgG2c CSR and B-cell intrinsic MyD88 is required for IFN-γ production. Moreover, IFN-γ receptor (IFNγR) deficiency abolished sHZ-induced IgG2c production, while recombinant IFN-γ administration successfully rescued IgG2c CSR impairment in mice lacking B-cell intrinsic MyD88. Together, our results show that B cell-intrinsic MyD88 signaling is involved in the MOA of certain particulate adjuvants and this may enhance our specific understanding of how adjuvants and vaccines work.
Identifiants
pubmed: 31087643
doi: 10.1002/eji.201848084
doi:
Substances chimiques
Adjuvants, Immunologic
0
Immunoglobulin G
0
Myd88 protein, mouse
0
Myeloid Differentiation Factor 88
0
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1433-1440Informations de copyright
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Références
Ishii, K. J. and Akira, S., Toll or toll-free adjuvant path toward the optimal vaccine development. J. Clin. Immunol. 2007. 27: 363-371.
Cunningham, A. L., Garçon, N., Leo, O., Friedland, L. R., Strugnell, R., Laupèze, B., Doherty, M. et al., Vaccine development: From concept to early clinical testing. Vaccine 2016. 34: 6655-6664.
Onishi, M., Ozasa, K., Kobiyama, K., Ohata, K., Kitano, M., Taniguchi, K., Homma, T. et al., Hydroxypropyl-β-cyclodextrin spikes local inflammation that induces Th2 cell and T follicular helper cell responses to the coadministered antigen. J. Immunol. 2015. 194: 2673-2682.
Marichal, T., Ohata, K., Bedoret, D., Mesnil, C., Sabatel, C., Kobiyama, K., Lekeux, P. et al., DNA released from dying host cells mediates aluminum adjuvant activity. Nat. Med. 2011. 17: 996-1002.
Kuroda, E., Ishii, K. J., Uematsu, S., Ohata, K., Coban, C., Akira, S., Aritake, K. et al., Silica crystals and aluminum salts regulate the production of prostaglandin in macrophages via NALP3 inflammasome-independent mechanisms. Immunity. 2011. 34: 514-526.
Gavin, A. L., Hoebe, K., Duong, B., Ota, T., Martin, C., Beutler, B. and Nemazee, D. Adjuvant-enhanced antibody responses in the absence of toll-like receptor signaling. Science (80-.). 2006. 314: 1936-1938.
Franchi, L. and Núñez, G., The Nlrp3 inflammasome is critical for aluminum hydroxide-mediated IL-1beta secretion but dispensable for adjuvant activity. Eur. J. Immunol. 2008. 38: 2085-2089.
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.
Coban, C., Igari, Y., Yagi, M., Reimer, T., Koyama, S., Aoshi, T., Ohata, K. et al., Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9. Cell Host Microbe. 2010. 7: 50-61.
Onishi, M., Kitano, M., Taniguchi, K. and Homma, T., Hemozoin is a potent adjuvant for hemagglutinin split vaccine without pyrogenicity in ferrets. Vaccine. 2014. 32: 3004-3009.
Tougan, T., Aoshi, T., Coban, C., Katakai, Y., Kai, C., Yasutomi, Y., Ishii, K. J. et al., TLR9 adjuvants enhance immunogenicity and protective efficacy of the SE36/AHG malaria vaccine in nonhuman primate models. Hum. Vaccines Immunother. 2013. 9: 283-290.
Uraki, R., Das, S. C., Hatta, M., Kiso, M., Iwatsuki-Horimoto, K., Ozawa, M., Coban, C. et al., Hemozoin as a novel adjuvant for inactivated whole virion influenza vaccine. Vaccine 2014. 32: 5295-5300.
Lee, M. S. J., Igari, Y., Tsukui, T., Ishii, K. J. and Coban, C., Current status of synthetic hemozoin adjuvant: A preliminary safety evaluation. Vaccine 2016. 34: 2055-2061.
Coban, C., Ishii, K. J., Kawai, T., Hemmi, H., Sato, S., Uematsu, S., Yamamoto, M. et al., Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin. J. Exp. Med. 2005. 201: 19-25.
Nutt, S. L. and Tarlinton, D. M., Germinal center B and follicular helper T cells: siblings, cousins or just good friends? Nat. Immunol. 2011. 12: 472-477.
Reiling, N., Ehlers, S. and Hölscher, C., MyDths and un-TOLLed truths: sensor, instructive and effector immunity to tuberculosis. Immunol. Lett. 2008. 116: 15-23.
Hou, B., Saudan, P., Ott, G., Wheeler, M. L., Ji, M., Kuzmich, L., Lee, L. M. et al., Selective utilization of toll-like receptor and Myd88 signaling in B cells for enhancement of the antiviral germinal center response. Immunity 2011. 34: 375-384.
Schenten, D., Nish, S. A., Yu, S., Yan, X., Lee, H., Brodsky, I., Pasman, L. et al., Signaling through the adaptor molecule MyD88 in CD4+ T cells is required to overcome suppression by regulatory T cells. Immunity 2014. 40: 78-90.
van Lieshout, M. H. P., Anas, A. A., Florquin, S., Hou, B., van't Veer, C., de Vos, A. F. and van der Poll, T., Hematopoietic but not endothelial cell MyD88 contributes to host defense during gram-negative pneumonia derived sepsis. PLoS Pathog. 2014. 10: e1004368.
Palm, N. W. and Medzhitov, R., Immunostimulatory activity of haptenated proteins. Proc. Natl. Acad. Sci. USA 2009. 106: 4782-4787.
LaRosa, D. F., Stumhofer, J. S., Gelman, A. E., Rahman, A. H., Taylor, D. K., Hunter, C. A. and Turka, L. A., T cell expression of MyD88 is required for resistance to Toxoplasma gondii. Proc. Natl. Acad. Sci. USA 2008. 105: 3855-3860.
Asano, K., Kikuchi, K. and Tanaka, M., CD169 macrophages regulate immune responses toward particulate materials in the circulating fluid. J. Biochem. 2018. 164: 77-85.
Gaya, M., Barral, P., Burbage, M., Bruckbauer, A. and Strid, J., Initiation of antiviral B Cell immunity relies on innate signals from spatially positioned NKT cells article initiation of antiviral B cell immunity relies on innate signals from spatially positioned NKT cells. Cell. 2018. 172: 517-533.
Rookhuizen, D. C. and DeFranco, A. L. Toll-like receptor 9 signaling acts on multiple elements of the germinal center to enhance antibody responses. Proc. Natl. Acad. Sci. USA 2014. 111:E3224-E3233.
Finkelman, F. D., Katona, I. M., Mosmann, T. R. and Coffman, R. L. IFN-gamma regulates the isotypes of Ig secreted during in vivo humoral immune responses. J. Immunol. 1988. 140: 1022-1027.
Harris, D. P., Goodrich, S., Gerth, A. J., Peng, S. L. and Lund, F. E., Regulation of IFN-γ production by B effector 1 cells: Essential roles for T-bet and the IFN-γ receptor. J. Immunol. 2005. 174: 6781-6790.
Barr, T. A., Brown, S., Mastroeni, P. and Gray, D., B cell intrinsic MyD88 signals drive IFN-gamma production from T cells and control switching to IgG2c. J. Immunol. 2009. 183: 1005-1012.
Kawai, T. and Akira, S., The role of pattern-recognition receptors in innate immunity: update on toll-like receptors. Nat. Immunol. 2010. 11: 373-384.
Sun, D. and Ding, A., MyD88-mediated stabilization of interferon-gamma-induced cytokine and chemokine mRNA. Nat. Immunol. 2006. 7: 375-381.
He, B., Santamaria, R., Xu, W., Cols, M., Chen, K., Puga, I., Shan, M. et al., The transmembrane activator TACI triggers immunoglobulin class switching by activating B cells through the adaptor MyD88. Nat. Immunol. 2010. 11: 836-845.
Sakaguchi, M., Murata, H., Yamamoto, K., Ono, T., Sakaguchi, Y., Motoyama, A., Hibino, T. et al., TIRAP, an adaptor protein for TLR2/4, transduces a signal from RAGE phosphorylated upon ligand binding. PLoS One. 2011. 6: e23132.
Castigli, E., Scott, S., Dedeoglu, F., Bryce, P., Jabara, H., Bhan, A. K., Mizoguchi, E. et al., Impaired IgA class switching in APRIL-deficient mice. Proc. Natl. Acad. Sci. USA 2004. 101: 3903-3908.
Hamaguchi, Y., Xiu, Y., Komura, K., Nimmerjahn, F. and Tedder, T. F., Antibody isotype-specific engagement of Fcgamma receptors regulates B lymphocyte depletion during CD20 immunotherapy. J. Exp. Med. 2006. 203: 743-53.
Hobeika, E., Thiemann, S., Storch, B., Jumaa, H., Nielsen, P. J., Pelanda, R. and Reth, M., Testing gene function early in the B cell lineage in mb1-cre mice. Proc. Natl. Acad. Sci. USA 2006. 103: 13789-13794.
Cossarizza, A., Chang, H.-D., Radbruch, A., Andrä, I., Annunziato, F., Bacher, P., Barnaba, V. et al., Guidelines for the use of flow cytometry and cell sorting in immunological studies. Eur. J. Immunol. 2017. 47: 1584-1797.
Shinnakasu, R., Inoue, T., Kometani, K., Moriyama, S., Adachi, Y., Nakayama, M., Takahashi, Y. et al., Regulated selection of germinal-center cells into the memory B cell compartment. Nat. Immunol. 2016. 17: 861-869.
Hayashi, M., Aoshi, T., Haseda, Y., Kobiyama, K., Wijaya, E., Nakatsu, N., Igarashi, Y. et al., Advax, a delta inulin microparticle, potentiates in-built adjuvant property of co-administered vaccines. EBioMedicine. 2016. 15: 127-136.
R Development Core Team. R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, Vienna). Available at http://www.R-project.org. Accessed June 21, 2016. 2016.
Culhane, A. C., Thioulouse, J., Perrière, G. and Higgins, D. G., MADE4: an R package for multivariate analysis of gene expression data. Bioinformatics. 2005. 21: 2789-2790.