4th Year MSTP
2nd Year Graduate Student
Advisor: Brian Sheridan, PhD, Stony Brook University
Department: Molecular Genetics and Microbiology
Graduate Program: Molecular Genetics and Microbiology
Title: Intestinal CD4 T cell response to oral Listeria monocytogenes infection
Abstract:
Pedro E Perez, Zhijuan Qiu, Brian Sheridan
CD4 T cells play a key multifactorial role in cell and humoral-mediated immunity against enteric pathogens. However, the exact mechanisms mediating short and long-term protection in intestinal tissue have not been extensively studied. The foodborne pathogen, Listeria monocytogenes (LM), is an intracellular gram-positive bacterium used to study different facets of the innate and adaptive immune responses. Prior studies have focused in elucidating the immune response to intravenous LM infection, however this type of systemic response greatly differs than that elicited by a natural oral route of infection. Our lab uses an oral feeding model with a ‘murinized’ LM that mimics human infection letting us interrogate the natural CD4 T cell response as well as long-term CD4 T cell memory formation to an enteric infection in intestinal tissues. Preliminary experiments have confirmed a mouse CD4 TCR transgenic (Tg) T cell line specific to the immunodominant MHC II-restricted listeriolysin epitope (LLO190-205) as a viable model to assess antigen-specific CD4 T cell responses during primary and memory phases of the T cell immune response. Further preliminary experiments showed that endogenous CD4 T cell depletion significantly increases mesenteric lymph node bacterial burden to a similar extent as CD8 T cell depletion. Moving forward we will establish the effect that CD4 T cell depletion has on other key mediators of the immune response to determine whether memory CD4 T cells act as resident sentinels that can ‘sense and alarm’ immune function. In addition, we will use our Tg T cell transfer model in order to better understand the direct and indirect mechanisms used by antigen-specific CD4 T cells to confer protection against oral LM infection.
