Project 462797

The development of our immune system depends on the microbiota, the collection of all microorganisms living on our body's surfaces. The impact of prokaryotic member in our microbiota on the host immune system are increasingly appreciated, however, our understanding of how eukaryotic members of the microbiota impact the host's immune system remain vastly enigmatic. Besides fungi and worms, protozoa are an increasingly recognized group of eukaryotic microbes that contain permanent members of the healthy intestinal microflora. The protozoan kingdom contains well-known pathogens, transiently colonizing the host's intestinal tract while causing moderate to severe damage. In contrast, a larger group of protozoan representatives permanently colonize the human and murine intestinal tract without recognizable damage to the host. Our laboratory identified that Tritrichomonads are such peaceful protozoan commensals that impact disease outcomes in mice. Here, we propose to investigate the role of Tritrichomonads as permanent members of the gut microflora on: 1. The innate immune system 2. The mucosal antibody response 3. The impact on the host's disease tolerance We will use a combination of genetic mouse models, adoptive cell transfer systems, single cell gene expression experiments, as well as cellular and biochemical assays to characterize the protozoan-regulation of the mucosal immune landscape and its capability to modulate short- and long-term disease outcomes during acute and chronic disease of the mucosa. Understanding the contributions of the microbiota to health has to extend towards investigations on protozoa as eukaryotic representatives. We are convinced that our proposal will allow us to identify new modes of host-microbe interactions that shape the host's immune landscape and work as architects of the body's defense mechanisms to confer protecting against acute and chronic inflammation.