Katherine L. Knight, PhD
Professor and Chair
Microbiology & Immunology
Research Interests:
- B-lymphocyte development and generation of the antibody repertoire.
Education
Ph.D., Indiana University
Research Interests
Knight Lab 2024
The Knight Lab is historically a B cell laboratory focused on how the B cell arm of the immune system contributes to health and disease. We focused on elucidating how B lymphocytes and the antibody repertoire develop in rabbits, as well as how commensal microbes affect this process. We discovered that commensal bacteria in the gut-associated lymphoid tissue (GALT) are required for both B cell development and for generation of a diverse antibody repertoire. This work led us to identify a harmless bacterium, Bacillus subtilis, which is involved in development and diversification of B cells in rabbits. Further, when introduced into mice this bacterium protects mice from allergic asthma, Traveler’s diarrhea and other T cell-mediated inflammatory diseases including graft vs host disease, and autoimmunity. As described below, we are investigating the mechanism by which Bacillus subtilis protects the host from a wide variety of inflammatory diseases.
Host-microbe interactions that prevent inflammatory diseases.
As stated above, in our studies to understand how intestinal bacteria promote development of the antibody repertoire in GALT, we identified B. subtilis as a commensal bacteria that can protect the host from disease caused by pathogenic organisms. We identified the active molecule of B. subtilis as exopolysaccharide, EPS, and we use a mutant strain of B. subtilis that secretes EPS into the culture medium, allowing us to easily purify the EPS. Using purified EPS, we found that it functions to protect from disease by inducing anti-inflammatory macrophages and tolerogenic dendritic cells, which inhibit T cell proliferation. Our goal is to determine the mechanism by which B. subtilis EPS protects from a variety of T cell-mediated diseases, including infectious diseases, allergy, autoimmunity, and graft-vs host disease. For these studies, we perform both in vivo and in vitro experiments. For in vivo work, we use normal and gene-specific knock-out mice, and for in vitro studies, we cell culture techniques, CRISPR, molecular biology techniques, flow cytometry, ELISA, western blots, and immunochemical methods. The focus of the studies is to identify the molecular pathway by which EPS induces an anti-inflammatory state, and how this can be used to prevent and treat numerous T cell mediated diseases.
Trained immunity.
Immunologic memory allows organisms to rapidly respond to pathogens and other previously encountered antigens. Memory within the adaptive immune system is well documented and understood. In contrast, memory within the innate immune system, termed trained immunity, has only recently gained full recognition, and is not well understood. Trained immunity is mediated by innate cells such as myeloid cells, and we use EPS derived from B. subtilis to study how trained immunity is induced, how long it is maintained, and the molecular mechanism for protection by “trained” myeloid cells. For these studies, we perform a combination of in vivo and in vitro experiments, and as above, we use normal and gene-specific knock-out mice, CRISPR, molecular biology techniques, tissue culture and immunoassays, including flow cytometry. Results from these studies will identify new therapeutic targets for preventing and treating inflammatory diseases.
Clostridium difficile infection (CDI). The major hospital-acquired infection in the U.S. is caused by the enteric pathogen C. difficile which leads to untold misery from colitis. In collaboration with Dr. Qiao in our Department, we are using papillomavirus- like particles to develop a mucosal vaccine to prevent CDI. We develop papillomavirus- like particles that encode specific pathogenic molecules of C. difficile, and use these to mucosally immunize mice. Mice are then orally challenged with C. difficile and analyzed for high antibody titers, decreased symptoms of colitis, and decreased colonization of C. difficile in the colon.
Publications/Research Listings
Full list of Katherine L. Knight Publications found in NIH National Library of Medicine
https://pubmed.ncbi.nlm.nih.gov/?term=Katherine+L+Knight