Development and function of humoral immunity in the Jamaican fruit bat, Artibeus jamaicensis

牙买加果蝠 Artibeus jamaicensis 体液免疫的发育和功能

• 批准号: 10576977
• 负责人: Hannah Kim Frank
• 金额: $ 15.2万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-18 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10576977
• 关键词: Adaptive Immune System; Address; Affinity; Aliquot; Animals; Antibodies; Antibody Repertoire; Antibody Response; Antibody titer measurement; Antigens; Avidity; B-Cell Antigen Receptor; B-Cell Development; B-Lymphocyte Subsets; B-Lymphocytes; Binding; Biological Assay; Blood specimen; Body Size; Cell Culture Techniques; Cells; Cellular Immunity; Central America; Chiroptera; Clonal Expansion; Clone Cells; Communicable Diseases; Comparative Genomic Analysis; DNA; Data; Development; Disease; Exposure to; Fever; Frequencies; Fruit; Future; Gene Combinations; Gene Rearrangement; Genes; Genetic; Genetic Recombination; Genomic DNA; Genomics; Health; Human; Humoral Immunities; Immune; Immune response; Immune system; Immunity; Immunoglobulin Class Switching; Immunoglobulin G; Immunoglobulin Isotypes; Immunoglobulin Somatic Hypermutation; Immunoglobulin Switch Recombination; Immunoglobulins; Immunologic Memory; Immunologics; Individual; Infection; Intervention; Investigation; Jamaican; Knowledge; Malignant Neoplasms; Marburgvirus; Measures; Mediating; Memory; Memory B-Lymphocyte; Monitor; Mutate; Mutation; Natural Immunity; Neutralization Tests; Organ; Organism; Population; Prevention; Public Health; Rabies; Rabies virus; Reagent; Research; Research Personnel; Role; SARS coronavirus; Serology; Somatic Mutation; South America; T-Lymphocyte; Techniques; Testing; Time; Vaccinated; Vaccination; Vaccines; Viral; Virus; Virus Diseases; Zoonoses; adaptive immunity; bat-borne; cell mediated immune response; cell type; cohort; experience; experimental study; immunoglobulin receptor; improved; insertion/deletion mutation; insight; next generation; pathogen; peripheral blood; prevent; receptor; response; transcriptome; transcriptomics

Project Summary Bats host many viruses, seemingly without disease, that cause lethal infections in humans and other non-bat species, including rabies, Marburg fever virus and SARS-related coronaviruses. A greater understanding of the bat immune system – how it responds to viruses, how it differs from the human immune system – could lead to improved approaches for treating or even avoiding infection in humans. The immune response consists of two major branches: the nonspecific innate response and the pathogen-specific adaptive response. Although numerous studies have investigated innate immunity in bats, very little is known about their adaptive immune system. The long-term objective of the proposed research is to enhance understanding of adaptive immunity in bats. A key feature of adaptive immunity is humoral immunity; this immune response is mediated by antibodies, also known as immunoglobulins. The hyper-diverse immunoglobulin repertoire is generated through a combination of gene recombination, DNA insertions and deletions, and somatic mutation of the antibody sequence. While immunoglobulins have been detected in several serological studies of bats, the true extent of the diversity of bat immunoglobulin repertoires, the degree to which bats rely on gene rearrangement vs. somatic mutation to generate these repertoires, how mutation of the immunoglobulins correlates with neutralization of pathogens, or the B cell subsets that arise in response to infection remain unknown. The proposed study will use rabies virus vaccination followed by rabies virus infection in Jamaican fruit bats to generate the most comprehensive understanding of B cell-mediated adaptive immunity in bats to date. Jamaican fruit bats are common across Central and South America, where rabies remains a serious threat, and are naturally infected by rabies virus. This research will use long-read sequencing to characterize the germline genes that provide the starting diversity for the immunoglobulin repertoire. Next generation genomic techniques will be used to track the development of rearranged immunoglobulin repertoires, monitor expansion of specific B cell clones, and quantify the degree of somatic mutation in antigen-exposed antibodies across vaccination and challenge with rabies. Single-cell transcriptomics will be used to characterize the B cell subsets that arise in response to immune challenges, and binding assays and rabies neutralization tests will facilitate an understanding of how antibody maturation correlates with function. Comparison of the immune responses of bats to vaccination and infection will be used to investigate immunity in controlled and natural contexts. This research will provide important information on the adaptive immune system of bats that is currently lacking. These data will provide insight into the differences in immune responses between bats and humans to a shared pathogen and can be used to develop new rabies prevention or intervention approaches. The framework and immunological data generated by this project will also allow for specific investigations of B-cell mediated immunity to any infection.

项目总结