John-Demian (JD) Sauer, PhD

Portrait of John-Demian (JD) Sauer, PhD
Assistant Professor
Medical Microbiology and Immunology
Address: 
4203 MSB
1550 Linden Drive
Madison, WI 53706
Telephone: 
(608) 263-1529
Focus Groups: 
Immunology/Immunopathology
Education: 
Ph.D. Microbiology and Immunology, Dr. Michele Swanson's Lab, University of Michigan, Ann Arbor, MI
Postdoctoral Fellow, Dr. Daniel Portnoy's Lab, University of California, Berkeley, CA
Research Summary: 
Bacterial Pathogenesis, Innate immunity, Cell Mediated Immunity
Research Detail: 

We are interested in three separate but related questions:

  1. how do intracellular pathogens parasitize their host cells
  2. how does the host recognize infection by intracellular pathogens
  3. how does recognition of intracellular pathogens by the innate immune system drive adaptive immune responses

Intracellular pathogens are a major cause of morbidity and mortality world-wide, including the important pathogens Mycobacterium tuberculosis, Plasmodium falciparum (malaria) and HIV. We utilize Listeria monocytogenes 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 as well as illuminating some of our macrophages 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 similarly use bacterial mutants to study host innate immune signaling pathways both to understand 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 continued use of L. monocytogenes as an immunotherapeutic platform.

Selected Publications: 
Witte, C.E., Archer, K.A., Rae, C.S., Sauer, JD, Woodward, J.J. and Portnoy, D.A. Innate Immune Pathways Triggered by Listeria monocytogenes and Their Role in the Induction of Cell-Mediated Immunity. Advances in Immunology. 113:135-56, 2012 PMCID N/A, PMID22244582
Sauer, JD., Sotelo-Troha, K., Brubaker, S.W., von Moltke, J., Monroe, K.M., Rae, C., Hyodo, M., Hayakawa, Y., Woodward, J.J., Portnoy, D.A., Vance, R.E. The ENU-induced Goldenticket (Gt) mouse mutant reveals an essential function of Sting(Tmem173, Mita, Mpys, Eris) in the in vivo interferon response to Listeria monocytogenes and cyclic-di-nucleotides. Infection and Immunity. 79(2):688-94, 2011 PMC3028833
Lightfield, K.L., Persson, J., Trinidad, N.J., Brubaker, S.W., Kofoed, E.M., Sauer, JD, Dunipace, E.A., Warren, S.E., Miao, E.A., Vance, R.E. Differential requirements for Naip5 in activation of the Nlrc4 (Ipaf) inflammasome. Infection and Immunity. 79(4):1606-14, 2011 PMC3067563
Sauer, JD., Peryere, S., Archer, K.A., Hanson, B., Lauer, P., Portnoy, D.A. Listeria monocytogenes engineered to activate the Nlrc4 inflammasome are severely attenuated and fail to induce protective immunity. Proc. Natl. Acad. Sci. USA. 108(30): 12419-12424, 2011. PMC3145703
Henry, T., Kirimanjeswara, G.S., Jones, J.W., Sauer, JD, Iwakura, Y., Metzger, D.W., Monack, D.M. Type I Interferon signaling constrains IL-17A/F secretion by gd T-cells during bacterial infections. Journal of Immunology. 184(7):3755-3767, 2010 PMC2879123
Sauer, JD., Witte, C.E., Zemansky, J., Hanson, B., Lauer, P., Portnoy, D.A. Listeria monocytogenes triggers AIM2-mediated pyroptosis upon infrequent bacteriolysis in the macrophage cytosol. Cell Host & Microbe.7(5):412-419, 2010 PMC2947455