The commensal bacteria that colonize the neonatal gastrointestinal tract may exert long lasting effects on the immune system, as alterations in the neonatal microbiota have been associated with the development of diseases later in life such as asthma, allergy, or inflammatory bowel disease. However, little is known about the antigen-specific immune response to neonatal commensal bacteria. The premise of this grant, therefore, is that determining the initial antigen-specific T and B cell response to commensal bacteria is fundamental to understanding how neonatal commensal bacteria may exert long-lasting effects on the immune system. Here, we will leverage our experience with TCR repertoires and commensal bacterial reactivity in adult mice to characterize to T cell response in neonates (Aim 1). We will also examine the role of maternal IgA and how it affects the early T and B cell response (Aim 2). Finally, we will ask whether these early adaptive responses are disrupted by ante-partum antibiotics or neonatal infections, potentially setting the stage for abnormal mucosal immune homeostasis (Aim 3). Thus, these data will generate a deeper understanding of the antigen-specific neonatal immune response and its unique role in the ontogeny of the immune system.
The commensal bacteria that colonize the neonatal gastrointestinal tract may exert lasting effects on the immune system, as alterations in the neonatal microbiota have been associated with the development of diseases such as asthma, allergy, and inflammatory bowel disease later in life. However, our understanding of whether antigen specific immune cells such as T and B cells interact with little commensal bacteria during the neonatal period is incomplete. The goal of this study is to address the fundamental question of whether T and B cells in the gut recognize commensal bacteria during the neonatal period of life, and if so, determine whether these interactions result in long lived cells that could have lasting effects on the immune system.
