María C López, PhD

The gut-associated immune system protects the host against orally invasive pathogens while mounting tolerance towards a myriad of commensal bacteria and food antigens to avoid unnecessary inflammation and food allergies.  Severe combined immunodeficient babies or immunosuppressed patients, either children or adults, who undergo bone marrow transplantation and suffer graft vs. host disease, have increased morbidity due to the lack of a functional gastrointestinal immune system.  These patients lack SIgA in their gut.  Our experimental model of hematopoietic stem cell transplantation uses immunodeficient mice (NOD/SCID/IL-2R common γ chain KO) reconstituted with human cord blood stem cells to investigate the development of a human immune system in the gut of an immunodeficient host. This model allows mechanistic determination of the conditions necessary to successfully generate (or recover) human SIgA in the gut lumen. Additionally, interventions that can most efficiently promote recovery of mucosal immunity can be investigated for improved protection of the host from opportunistic infections of the gastrointestinal tract.   Furthermore, the knowledge acquired provides a better understanding of the mechanisms behind mucosal immune alterations that can lead to food allergies and malnutrition.  Our experimental model of chronic alcohol administration uses young healthy mice to study how alcohol consumption alters gut immunity and the gut microbiome. This investigation aims to understand the mechanisms altered by alcohol consumption that facilitate infections.