Department: Medical Microbiology and Immunology
Immunology Focus area: Host-Pathogen Interactions, Tumor Immunology
Descriptive Title of Research: Influence of cytosolic innate immune activation on generation of cell mediated immunity
Research Description:
The focus of our lab revolves around understanding host pathogen interactions. Specifically we are interested in three separate but related questions:
- How do intracellular pathogens parasitize their host cells?
- How does the host recognize infection by intracellular pathogens?
- How does recognition of intracellular pathogens by the innate immune system drive adaptive immune responses?
Intracellular pathogens, including Mycobacterium tuberculosis, Plasmodium falciparum (malaria) and HIV, are a major cause of morbidity and mortality world-wide. We predominantly utilize Listeria monocytogenes, an important foodborne pathogen and a model organism, to understand how intracellular pathogens parasitize their host cells and how the host responds to infection.
Specifically, we are interested in understanding what virulence factors allow L. monocytogenes to survive and thrive in the cytoplasm of normally bactericidal macrophages. A major direction of our lab is the use of genetic screens to identify L. monocytogenes mutants with defects in survival or replication within the macrophage cytoplasm. Identification of these specific adaptations will allow for the development of novel antimicrobial intervention strategies in addition to illuminating some of our macrophage’s normal defense mechanisms.
In addition to identifying bacterial factors necessary for causing disease, we are interested in the mechanisms the host uses to detect intracellular pathogens. We have used bacterial genetic screens to study host innate immune signaling pathways to understand both how they are stimulated and what the consequences of their activation are. We are interested in understanding what role innate immune signaling pathways, specifically inflammasome activation and type I interferon induction, play in controlling acute infections and in driving the development of robust cell mediated immune responses. To address these questions we utilize a combination of bacterial and mouse mutants to dissect the role of individual signaling pathways in the development of CD8+ T-cell responses to L. monocytogenes infection. Understanding how cell mediated immune responses are generated is key to the development of novel vaccines and therapeutics targeting intracellular pathogens and tumors
Link to Publications: PubMed Link Publications
Graduate Program Affiliations: MDTP, CMB, CMP, MCP
Lab Website: https://sites.google.com/view/sauerlabwisc/home