Goldberg Lab

Innate Immune Responses to Bacterial Pathogens

Image of four macrophages undergoing pyroptosis. Detected by green fluorescence signal are ASC specks in the macrophage cytosol.

In addition to infecting intestinal epithelial cells, Shigella infect macrophages within the intestinal lamina propria and Peyer’s patches. Macrophages are both activated and killed by intracellular Shigella. Macrophage respond by GBP-dependent recognition of Shigella and inflammasome activation, which triggers the release of pro-inflammatory cytokines and inflammatory cell death. From a genetic screen, we discovered a role for human proteins not previously known to contribute to these innate immune responses. Using cell biology, protein biochemistry, and primary and cell culture-based assays, we are working to uncover the mechanisms by which these, other host factors, and bacterial proteins contribute to innate immune responses. 

Diagram of the intestinal epithelium, containing epithelial cells and M cells. Beneath the epithelium are macrophages, which when infected by Shigella, die via pyroptosis.