Projects and Grants per year
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.
Status | Finished |
---|---|
Effective start/end date | 3/1/20 → 2/28/23 |
Funding
- National Institute of Allergy and Infectious Diseases
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Projects
- 1 Finished
-
Defining the Intracellular Growth Niche of Foodborne Listeria Monocytogenes
D'Orazio, S. (PI)
National Institute of Allergy and Infectious Diseases
3/1/20 → 2/29/24
Project: Research project