Seminar-The First Line of Defense: The role of epithelial cell inflammasomes in controlling Campylobacter jejuni infection
presents a seminar by:
Campylobacter jejuni is the most common cause of infectious gastroenteritis in the developed world yet many aspects of its colonization and infection of the gut remain poorly defined. One cryptic aspect of its pathogenesis is C. jejuni’s’s ability to invade intestinal epithelial cells as it colonizes and infects the host intestine. Our work has illustrated that C. jejuni has the capacity to invade intestinal epithelial cells in the mammalian gut near the apical ends of intestinal crypts, where it resides within LAMP-1 positive vesicles. Using a combination of knockout mouse models and an in vitro primary epithelial cell model, we now illustrate the role of epithelial cell intrinsic inflammasomes in controlling Campylobacter cell invasion during the course of infection. Mice lacking key inflammasome components, including Asc or Caspase 1, lose much of their ability to limit C. jejuni invasion and replication inside of intestinal epithelial cells. This allows C. jejuni to replicate to large numbers inside of these LAMP1 positive vesicles, from where they can be released back into the intestinal lumen and infect additional epithelial cells. The consequences of impaired inflammasome function include increased pathogen burdens, a prolonged course of infection and significantly increased pathology in infected mice. Conversely, mice with functional epithelial cell inflammasomes effectively control the number of intracellular bacteria and exhibit only moderate infection induced pathology and pathophysiology. Although much remains to be discovered regarding the role of epithelial cell invasion in C. jejuni pathogenesis, these findings highlight the importance of epithelial cells as an active player in combating this important enteric pathogen.
The Department of Microbiology and Immunology