B Cell/T Cell Interactions in Brucellosis

Document text

Principal Investigator: Jerod  Skyberg
Organization: UNIVERSITY OF MISSOURI-COLUMBIA
Fiscal Year: 2024
Award: $383,747
Funding agency: National Institute of Allergy and Infectious Diseases

Project Summary/Abstract
 In humans, Brucella spp. can cause a lifelong, debilitating disease, with relapses of undulating fever and
other complications even with antibiotic treatment. No vaccines are currently licensed to prevent human
brucellosis, and mechanisms underlying the ability of Brucella to cause chronic infection are not well known. We
have found B cells enhance susceptibility to Brucella infection by inhibiting CD4+ T cell-mediated immunity. In
this proposal, we will test the hypothesis that B cell antigen presentation skews the CD4+ T cell response during
brucellosis which impairs vaccine efficacy and contributes to chronicity of infection. In Aim #1 of this proposal
we will investigate mechanisms by which B cell antigen presentation affects control of infection and modulates
differentiation of CD4+ T cells into Th1, Th17, or regulatory T cells. In Aim #2 of this proposal, we determine how
follicular interactions between B and CD4+ T cells affect antibody production and CD4+ T cell function and
determine the relative contribution of IgG and IgM to immunity to infection. Collectively, our results will enhance
our knowledge of the pathogenesis of chronic brucellosis and identify immunomodulatory strategies that can be
incorporated into the rational design of brucellosis vaccines

Terms: <19S Gamma Globulin><7S Gamma Globulin><Ab response><Adoptive Transfer><Affect><Animals><Antibiotic Therapy><Antibiotic Treatment><Antibodies><Antibody Formation><Antibody Production><Antigen Presentation><Antigen-Presenting Cells><Antigens><B blood cells><B cell><B cell receptor><B cells><B-Cell Antigen Receptor><B-Cell Deficiency><B-Cells><B-Lymphocytes><B-cell><BLR1><BLR1 gene><Bone Marrow><Bone Marrow Reticuloendothelial System><Brucella><Brucella Vaccine><Brucellosis><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><CSIF><CSIF-10><CXCR-5><CXCR5><Cell Communication><Cell Communication and Signaling><Cell Function><Cell Interaction><Cell Mediated Immunology><Cell Physiology><Cell Process><Cell Signaling><Cell-Mediated Immunity><Cell-to-Cell Interaction><Cellular Function><Cellular Immunity><Cellular Physiology><Cellular Process><Chimera><Chimera organism><Chronic><Class Switching><Class Switchings><Cytokine Synthesis Inhibitory Factor><Data><Development><Disease><Disorder><FOXP3><FOXP3 gene><Fever><Forkhead Box P3><Future><Goals><Homing><Human><IL-10><IL10><IL10A><IgG><IgM><Immunity><Immunoglobulin Class Switching><Immunoglobulin Class Switchings><Immunoglobulin G><Immunoglobulin M><Impairment><Infection><Infection Control><Interleukin 10 Precursor><Interleukin-10><Intracellular Communication and Signaling><Isotype Switching><Isotype Switchings><JM2><Knowledge><Licensing><MDR15><Malta Fever><Mediating><Mice><Mice Mammals><Modern Man><Murine><Mus><Mutant Strains Mice><Pathogenesis><Phenotype><Predisposition><Production><Public Health><Pyrexia><Receptor Signaling><Regulatory T-Lymphocyte><Relapse><Resistance><Role><SCURFIN><Signal Transduction><Signal Transduction Systems><Signaling><Sterility><Subcellular Process><Susceptibility><T cell response><T-Cell Activation><T-Cell Development><T-Cell Ontogeny><T-Cells><T-Lymphocyte><T-Lymphocyte Development><T4 Cells><T4 Lymphocytes><Teff cell><Testing><Treg><Undulant Fever><Vaccines><Zoonoses><Zoonotic><Zoonotic Infection><accessory cell><activate T cells><antibody biosynthesis><bacterial disease treatment><bacterial infectious disease treatment><biological signal transduction><chimeras><chronic infection><conditional mutant><conditional mutation><developmental><effector T cell><febrile><febris><humoral immunity deficiency><immune modulating strategy><immune modulatory strategy><immunogen><immunoglobulin biosynthesis><immunomodulatory strategy><improved><in vivo><mouse mutant><neglect><persistent infection><preservation><prevent><preventing><rational design><regulatory T-cells><resistant><social role><sterile><thymus derived lymphocyte><uptake><vaccine efficacy>