Exploring the mechanisms of bacterial virulence and host defense during enteric infection in adult and neonatal mice

Seminar Details
Wednesday, May 15, 2019 - 9:00am to 10:00am


Gustavo Caballero, Ph.D.
Research Fellow (Nunez Lab)


5623 Med. Sci. II  (Wheeler Seminar Room)

Gabriel Nunez, Ph.D.

Diarrheal disease is the second leading cause of child mortality and remains a major cause of adult morbidity worldwide, especially throughout developing countries. Diarrhea is usually the result of an infection in the intestinal tract, which can be caused by a variety of bacterial, viral and parasitic organisms. Among these, Enteropathogenic Escherichia coli (EPEC) and Enterohemorrhagic Escherichia coli (EHEC) are major causes of lethal infection and diarrheal disease in young children and adults, respectively. These pathogens induce ‘‘attaching and effacing’’ (A/E) lesions on the intestinal epithelium leading to transient enteritis or colitis in humans. Citrobacter rodentium has been extensively used as a surrogate model for studying the pathogenesis of human infections with EPEC and EHEC, for which there is no natural animal model of disease. Several studies have demonstrated the role of adaptive immunity in the control of C. rodentium infection, showing that pathogen-specific IgG antibodies are required for pathogen clearance and host survival in adult mice. However, the role of maternal IgG in neonatal host defense against C. rodentium remains poorly understood. Similarly, although it has been previously described that luminal C. rodentium are out competed by the gut microbiota during the eradication phase, the mechanisms by which the pathogen overcomes the colonization resistance imposed by the microbiota during early infection remain unclear. Using a maternal vaccination and neonatal infection model, we examined the mechanism by which maternal antibodies protect the offspring against C. rodentium. We show that maternal pathogen-specific IgG, delivered through breast milk into the neonatal intestinal lumen, plays a critical role in neonatal protection, and identified specific antigens for maternal vaccination and protection of the offspring. Using a robust high throughput approach, we have also evaluated the genetic determinants required for successful colonization of C. rodentium during early infection in the gut of adult mice.  Altogether, these studies provide important insight into the mechanisms of bacterial virulence, host defense and colonization resistance during infection in the gut both in adult and neonatal mice.