Project Details
Projekt
Generation of gnotobiotic mice to investigate the role of the intestinal microbiota in Salmonella enterica spp. I serovar Typhimurium colitis in AGR2-deficient mice
Applicant
Professorin Dr. Barbara Stecher-Letsch
Subject Area
Parasitology and Biology of Tropical Infectious Disease Pathogens
Term
from 2013 to 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 237281995
The intestinal microbiota plays a pivotal role in protection against the enteric Salmonella serovar Typhi-murium (S. Tm) infection. In mice, treatment with the antibiotic streptomycin transiently disrupts the microbiota and enables S. Tm colonization of the gut, tissue invasion and induction of intestinal inflam-mation. Besides the microbiota, the mucosal barrier significantly contributes to immediate immune de-fence against S. Tm. So far, the interplay of the microbiota and the innate immune system is poorly un-derstood. We analyzed S. Tm infection in mice deficient in anterior gradient 2 (AGR2), which have se-vere mucosal barrier defects. Yet, in opposition to our prediction, AGR2-/- mice were protected against S. Tm induced gut inflammation, in contrast to AGR2+/- littermate controls. AGR2-/- mice exhibited altered microbiota composition and increased microbiota density in response to streptomycin. Thus, we hypothe-size that imbalanced mucosal homeostasis in AGR2-/- mice induced microbiota alterations which provided increased resistance against S. Tm infection. In our case, the intestinal microbiota could compensate for mucosal barrier defects. In this proposal we aim at further characterizing the influence of altered mucosal homeostasis on the intestinal microbiota and how this is related to increased resistance against S. Tm in-fection. To dissect the effect of mucosal homeostasis and the microbiota on the outcome of S. Tm infec-tion, we aim to generate germfree and gnotobiotic AGR2-/- mice associated with a defined gut microbiota. To this end, we will apply a novel “Oligo-Mouse-Microbiota” developed in our laboratory.
DFG Programme
Priority Programmes
