Quality Control of Antibody Responses by the Innate Signaling Adaptor MAVS

通过先天信号转导适配器 MAVS 进行抗体反应的质量控制

• 批准号: 9978499
• 负责人: DOMINIK SCHENTEN
• 金额: $ 23.03万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9978499
• 关键词: Address; Advanced Development; Antibody Affinity; Antibody Formation; Antibody Response; Antigens; Attenuated Vaccines; B-Lymphocytes; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Cells; Cessation of life; Cytosol; Defect; Development; Disease; Epitopes; Expression Profiling; Family; Flavivirus; Foundations; Future; Gene Expression; Generations; Genes; Goals; Human; Humoral Immunities; Immune; Immune response; Immune system; Immunity; Impairment; Individual; Infection; Inflammatory; Innate Immune Response; Interferons; Investigation; Knowledge; Mediator of activation protein; Membrane; Microbe; Mitochondria; Modeling; Molecular; Mus; Myeloid Cells; Natural Immunity; Neurologic; Pattern recognition receptor; Quality Control; RNA; RNA Helicase; RNA Viruses; Recovery; Regulation; Regulatory T-Lymphocyte; Role; Signal Pathway; Signal Transduction; Structure of germinal center of lymph node; Subunit Vaccines; Symptoms; Testing; Toll-like receptors; Vaccine Design; Vaccines; Viral; Virus; Virus Diseases; West Nile viral infection; West Nile virus; Work; adaptive immune response; adaptive immunity; base; cytokine; design; flu; insight; microbial; mortality; mosquito-borne; mutant; neutralizing antibody; novel vaccines; pathogen; peroxisome; receptor; response; tool; transmission process

ABSTRACT Innate immune recognition of microbial compounds by pattern recognition receptors (PRRs) represents a central regulatory checkpoint in the control of adaptive immune responses. Rig-I-like receptors (RLRs) comprise a PRR family that includes the RNA helicases RIG-I and MDA-5. RLRs recognize microbial RNA species in the cytosol and rely on the essential signaling adaptor MAVS for the induction of the cellular response. RLRs are important mediators of innate immunity to multiple viral infections. However, the role of RLRs in the regulation of adaptive immunity is still poorly understood. MAVS-deficient mice infected with West Nile Virus (WNV) fail to develop an effective virus-specific neutralizing antibody response, suggesting an important role for MAVS signaling in the control of humoral immunity. Here, we will employ a single-round-of-infection mutant of WNV to probe the central hypothesis that RLRs regulate the quality control of the antibody response. Our study will therefore address fundamental mechanistic questions about the role of RLRs in the adaptive immune response to WNV and other RNA viruses. Such insights will advance the development of novel vaccine strategies against WNV and related flaviviruses.

摘要