Research
Balancing inflammation during infection
It is essential that our immune systems are able to sense and respond to pathogenic microbes to prevent them from causing disease. The type and magnitude of the immune response is critical for controlling their replication while minimizing the damage to the host. Balance is key: too little or the wrong type of inflammation and the host can fail to control the pathogen and may succumb to the infection. Too much inflammation will damage tissues and the host may succumb to immunopathology. Our lab is interested in understanding how these interactions between the host and pathogenic or commensal microbes serve to shape the mammalian immune system to effectively limit the replication of the microbes while minimalizing damage to infected tissues. More specifically, our research interests are focused on the mechanisms and consequences of innate immune sensing and signaling in response to a variety of microorganisms. A detailed mechanistic understanding of these processes can help to develop improved vaccination strategies, and identify targets for therapeutics to enhance or dampen the immune response in an appropriate and specific manner.
Immune responses to commensal vs pathogen microbes
The intestine presents a unique immunological environment where trillions of commensal microbes are constantly present and sensed by the immune system, yet the resulting inflammatory response must be minimal for the tissue to function and for the health of the host. Conversely, the intestinal immune system must be poised to respond to pathogenic microbes. Failure to maintain this balance can lead to inflammatory bowel diseases (IBD), such as Crohn’s Disease and Ulcerative Colitis. Therefore, sensing of both pathogenic and commensal microbes is essential for initiating immune responses of appropriate magnitudes to restrict their growth and spread. The transcription factor NF-κB plays a central role in the activation and modulation of the immune system, integrating signals from multiple receptors or “sensors”, including Toll-like receptors (TLRs), and receptors for cytokines such as TNFα and IL-1β. We have found that HOIL-1, a component of the Linear Ubiquitin chain Assembly Complex (LUBAC) that regulates NF-κB activation, differentially modulates inflammation in response to multiple different pathogens in mice. Similarly, HOIL-1 deficiency in humans is associated with an immune disorder involving auto-inflammation, immunodeficiency and IBD-like symptoms. Our current studies focus on dissecting the cellular and molecular mechanisms by which HOIL-1 and the LUBAC complex regulate intestinal homeostasis and inflammation in response to commensal and pathogenic microbes in the intestine.
MacDuff Lab
Department of Microbiology and Immunology
University of Illinois at Chicago College of Medicine
Mailing Address: 835 S. Wolcott Avenue, E704 MSB (MC790), Chicago, IL 60612
Lab Location: 909 S. Wolcott Avenue, Room 7168 COMRB, Chicago, IL 60612
Phone: 312-996-5763
Email: dmacduff@uic.edu