title: TLR7 recognition is dispensable for influenza virus A infection but important for the induction of hemagglutinin-specific antibodies in response to the 2009 pandemic split vaccine in mice.
abstract: Recognition of pathogen-associated molecular patterns by pattern recognition receptors of the innate immune system is crucial for the initiation of innate and adaptive responses and for immunological memory. We investigated the role of TLR7 in the induction of adaptive immunity and long-term memory following influenza virus infection and vaccination in C57BL/6 mice. During infection with influenza A/PR8/34 virus, the absence of either TLR7 or MyD88 leads to reduced virus-specific antibodies in the serum and antibody-secreting cells in their secondary lymphoid organs, particularly in bone marrow. In spite of this, the absence of TLR7/MyD88 signaling did not impair the production of protective antibodies. Following immunization with the 2009 pandemic inactivated split vaccine, TLR7(-/-) mice had significantly lower levels of germinal center formation, antibody-secreting cells, and circulating influenza virus-specific antibodies than control animals. Consequently, TLR7(-/-) mice failed to develop protective immunological memory upon challenge. Furthermore, the immunogenicity of the split vaccine was likely due to TLR7 recognition of virion RNA, as its removal from the split vaccine significantly reduced the levels of influenza virus-specific antibodies and compromised the vaccine protective efficacy in mice. Taken together, our data demonstrate that TLR7 plays an important role in vaccine-induced humoral immune responses to influenza virus through the interaction with viral RNA present in the split vaccine.
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors: Victoria
authors: V
authors: Jeisy-Scott
authors: Jin Hyang
authors: JH
authors: Kim
authors: William G
authors: WG
authors: Davis
authors: Weiping
authors: W
authors: Cao
authors: Jacqueline M
authors: JM
authors: Katz
authors: Suryaprakash
authors: S
authors: Sambhara
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D000921:Antibody-Producing Cells / Q000276:immunology; D018858:Germinal Center / Q000821:virology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D007156:Immunologic Memory; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D012367:RNA, Viral / Q000276:immunology / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000172:deficiency / Q000276:immunology* / Q000502:physiology
chemical_list: D000914:Antibodies, Viral; C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012367:RNA, Viral; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7