Brian Sheridan

Brian Sheridan Assistant Professor

Department of Microbiology and Immunology
Ph.D., Immunology, University of Pittsburgh School of Medicine, 2008

(631) 632-4459
(631) 632-4294



Center for Infectious Diseases


The major entry point for many human pathogens is through gastrointestinal mucosal surfaces. Thus, a goal of vaccination against foodborne pathogens is to block pathogen entry through the intestinal mucosa. Understanding the mechanisms of immunologic protection at this site is essential for designing effective vaccination schemes against mucosal infections. Despite this fact, our understanding of intestinal T cell responses remains incomplete. Understanding the processes of effector T cell generation, establishment of memory, and memory T cell maintenance within the intestinal mucosa will improve our ability to regulate intestinal inflammation and aid in rational vaccine design. The promise of Listeria as a vaccine platform is multidimensional and predominately being designed for use against various pathogens and cancers due to the robust immunological response Listeria induces.

My laboratories research focuses on elucidating the processes regulating immunologic memory in intestinal tissues using oral Listeria infection of mice. My lab utilizes a recombinant Listeria that can invade the intestinal epithelium of mice thereby recapitulating the physiologic route and entry point of Listeria in humans. Our model provides an excellent opportunity to understand the mechanisms of intestinal T cell immunity and identify paradigms that may apply to other mucosally acquired human pathogens and inflammatory disorders of the intestines.


I. Resident memory T cells (Trm) in the intestines
Oral infection with Listeria induces a robust intestinal CD8 T cell response that is critical for protection against a secondary oral infection. Intestinal effector CD8 T cells are predominately composed of memory precursor effector cells that rapidly upregulate CD103, which is important to promote T cell accumulation but is not critical for T cell retention in the intestinal epithelium in this model. The ability to form rapid and protective intestinal memory in the lamina propria and epithelial layer was dependent on T cell intrinsic signaling through the transforming growth factor-b (TGF-b) receptor. CD103 expression and memory development or maintenance did not occur in the absence of TGF-b signals. Future work will examine the factors that promote CD8 and CD4 T cell residency in the intestines with an emphasis on rationale vaccine design.

II. Memory gd T cells in mucosal inflammation
The study of T cell memory and the target of vaccine design have predominately focused on conventional T cells bearing an alpha beta (ab) T cell receptor. We have demonstrated that a distinct subset of nonconventional T cells bearing a gamma delta (gd) T cell receptor mounts an immune response to an oral infection. Surprisingly, these cells survived into memory and provided protection to repeated infections. These memory cells were multifunctional and displayed a contextual specificity to the infection. For example, memory cells generated to one pathogen would not recall to a distinct pathogen or to the same pathogen if infected by a different route. This was an unexpected finding for gd T cells. Importantly, memory gd T cells were able to provide enhanced protection against infection within the intestinal mucosa. These findings illustrate a previously unrecognized role for nonconventional memory T cell subsets in the intestinal mucosa. Little is known of this Lm-elicited unconventional T cell population and factors that regulate the establishment and maintenance of this population will be explored.