Research

Inflammasomes

Sensing platforms of the innate immune system are critical for orchestrating the communitcation between the human body and its microbial environment. We are studying the integrative activity of multiple such platforms at mucosal surfaces - the place of intimate contact between the host and the world surrounding it.

In particular, we are interested in the inflammasome, a protein complex of the innate immune system, which functions as a sensor of both microbial products and host-derived damage signals. Upon activation, NLR sensor proteins, adaptor proteins (ASC) and inflammatory caspases assemble to form the inflammasome (see Figure). Activation of the inflammasome leads to the catalytic processing of the cytokines IL-1 and IL-18, as well as to a peculiar form of cell death called pyroptosis.

 

 

 

 

 

 

 

 

 

 

We have identified the NLRP6 inflammasome as a novel critical regulator of host-microbial mutualism in the intestine. NLRP6 signaling in intestinal epithelial cells is required for maintaining a stable microbial composition in the intestine, and aberrations in this system lead to the outgrowth of bacterial species which are normally suppressed.

The balance between activation of the innate immune system and microbial colonization on mucosal surfaces is essential for health, as distortions in the balance can lead to the development of a multitude of diseases - ranging from chronic inflammatory disease to autoimmunity, obesity, and cancer. We are striving to decipher the mechanisms regulating the communitcation between the innate immune system, our microbial environment, and their effects on a variety of human diseases.