title: MyD88 plays an essential role in inducing B cells capable of differentiating into antibody-secreting cells after vaccination.
abstract: We investigated the roles of MyD88, an innate adaptor signaling molecule, in inducing protective humoral immunity after vaccination with influenza virus-like particles (VLPs). MyD88 knockout C57BL/6 mice (MyD88(-/-) mice) vaccinated with influenza VLPs showed significant defects in inducing IgG2a/c isotype antibodies and in generating splenic recall memory B cell responses and antibody-secreting plasma cells in the bone marrow. The protective efficacy of influenza VLP vaccination was lower in MyD88(-/-) mice than in the wild-type mice. Our findings indicate that MyD88-mediated innate signaling pathways are important for effectively inducing primary and boost immune responses, T helper type 1 isotype-switched antibodies, and gamma interferon (IFN-γ)-secreting T cell responses. In particular, the results in this study demonstrated for the first time that MyD88-mediated immune activation is likely an essential pathway for effective generation of long-lived antibody-secreting plasma cells and highly protective immunity after vaccination with influenza VLPs. This study provides insight into mechanisms by which recombinant viral vaccines induce protective immunity via the MyD88-mediated innate immune signaling pathway.
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA. skang24@gsu.edu
authors.forename: Sang-Moo
authors.initials: SM
authors.lastname: Kang
authors.forename: Dae-Goon
authors.initials: DG
authors.lastname: Yoo
authors.forename: Min-Chul
authors.initials: MC
authors.lastname: Kim
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Song
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Park
authors.forename: Eunju
authors.initials: E
authors.lastname: O
authors.forename: Fu-Shi
authors.initials: FS
authors.lastname: Quan
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Richard W
authors.initials: RW
authors.lastname: Compans
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000921:Antibody-Producing Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D022721:Vaccines, Virosome / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007252:Influenza Vaccines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D022721:Vaccines, Virosome; D007371:Interferon-gamma