Eric R. Houpt, MD
The Houpt laboratory has developed the mouse model for the tropical infection amebiasis. This work has shown the unexpected role of cell-mediated immunity on the outcome of infection, including exacerbation of disease by CD4+ cells, the salutary effect of IL-10 on natural resistance, and the maintenance of infection by an aberrant IL-4 response. The accumulated data suggests a “two-hit” model to pathogenesis. First the amoeba must establish infection by circumventing the epithelial barrier. Certain hosts are intrinsically resistant at this level through a mechanism that is contributed by IL-10 and abrogated by epithelial apoptosis. If successful at the epithelial level, the amoeba must then survive the ensuing adaptive immune response, whereby IFN-g is protective and IL-4 maladaptive. The laboratory also develops molecular diagnostic tools to aid enterics and tuberculosis research. Recently the lab has developed multiplexed, quantitative, PCR-based tools to detect the broad gamut of enteropathogens. These are then applied to field projects in Tanzania, Bangladesh, and elsewhere to define specific microbiologic contributions to diarrhea, malnutrition, and wasting. This requires both quantitative and subtyping capabilities because of the diverse and rich “background” level of enteropathogen colonization in many global communities. As an example, this work has revealed that Giardia subtype A is associated with diarrhea in Bangladesh, while subtype B is associated with carriage.