P26.00003. Visualizing and controlling immune response to gut microbes

Presented by: Brandon Schlomann


Abstract

Trillions of bacteria reside in the intestine where they are largely kept away from epithelial surfaces. When this spatial confinement is broken, the resulting immune responses can be damaging and lead to disease. Understanding the processes that spatially restrict gut bacteria will open new avenues for microbiome-based therapies. I will present work that investigates interactions between immune cells and resident gut bacteria through live imaging of naturally transparent, larval zebrafish. We discovered that flagella-based swimming motility enables a native Vibrio species to govern its own spatial organization within the gut and stimulate a potent immune response. Mutants that cannot swim become aggregated and confined to the interior lumen of the gut. Loss of motility also leads to reduced expression of the proinflammatory cytokine TNFα in gut-associated macrophages and in the liver. Externally-inducible genetic switches enabled in situ manipulation of bacterial motility, and therefore external control of both bacterial spatial distribution and proinflammatory potential. Our findings reveal connections between the physical activity of bacteria, their spatial organization, and host inflammatory activity.

Authors

  • Brandon Schlomann
  • Travis J Wiles
  • Elena S Wall
  • Karen Guillemin
  • Raghuveer Parthasarathy


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