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Résumé |
Inside the organism, the immune system can fight generically against any
bacteria. However, the lumen of the gut is home to a very important
microbiota, so the host has to find alternative ways to fight dangerous
bacteria while sparing beneficial ones. While many studies have focused on
the complex molecular and cellular pathways that trigger an immune
response, little is known about how the produced antibodies act once
secreted into the intestinal lumen. Our modeling work is along 3 axes.
First, using stochastic models of bacterial population dynamics and
branching processes, we infer relevant biological parameters of the
dynamics of the bacterial population in the in vivo experiments of our
collaborator, Emma Slack (ETH Zurich). We contributed to show that the main
physical effect of these antibodies is to cross-link bacteria into clusters
as they divide, preventing them from interacting with epithelial cells,
thus protecting the host. We then developed a simple ordinary differential
equations model of these bacterial clusters, and studied how the interplay
of the time scales of bacterial growth and of link breaking could enable
the immune system to target the most problematic bacteria. Last, we studied
how such immune-mediated bacterial clustering could impact the evolution of
drug resistance by using a hybrid cross-scale model (with deterministic
within-host bacterial growth, and stochastic transmission). |
