Diversity Supplement for Jamila Tucker: Defining the Intracellular Growth Niche of Foodborne Listeria monocytogenes

Grants and Contracts Details

Description

The primary goals of the funded application R21AI151482 are to identify the cell type(s) in the gut that support intracellular growth of Lm and to define the innate immune response of intestinal cell types that that interact primarily with either intracellular or extracellular Lm. We hypothesize that Lm initially interact primarily with cell types that that they cannot efficiently invade or survive in, and that later in the course of infection, the bacteria shift to a cell type that serves as a protected intracellular growth niche. In Aim 1, four candidate intestinal myeloid cell types (hematopoietic cells) will be sort purified, infected directly ex vivo and assayed for both intracellular localization and replication. In Aim 2, flow cytometry will be used to identify Lm-associated cells in the lamina propria and submucosa of the ileum and colon as well as the MLN that drain each of these tissues (SI-MLN and LI-MLN) to track the fate of Lm that invade the gut mucosa in mice. In Aim 3, we will define the initial response of all eight subsets of intestinal myeloid cells by measuring the production of cytokines known to be triggered by either host cell surface bound or cytosolic receptors. These exploratory studies will fill a key knowledge gap in the field by defining the early events that occur in the gut during foodborne transmission of Lm. The purpose of this diversity supplement application is to add an additional person to the grant (Jamila Tucker, a Black/African American current first year IBS student) to extend these studies by also investigating stromal cells in the MLN. Stromal cells provide structural support for lymphoid tissues, and can act as a scaffold to organize different subsets of lymphocytes. These nonhematopoietic cells are often overlooked when innate and adaptive immune responses, but their close proximity to infectious foci makes them an ideal candidate to be an intracellular growth niche for Lm. Jamila Tucker will test all four subsets of fibroblastic reticular cells in the MLN following the same basic approaches as outlined above in Aims 1,2, and 3. This work will provide Ms. Tucker with extensive expertise in flow cytometric analysis and cell sorting, as well as ex vivo assays to measure host-pathogen interactions, a skill set that will make her valuable to the Microbiology workforce.
StatusFinished
Effective start/end date3/1/202/28/23

Funding

  • National Institute of Allergy and Infectious Diseases

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