Principle Areas of Study
Define factors that regulate the immune response to carbohydrate antigens
Although adaptive immunity possesses the ability to respond to a nearly infinite range of antigenic determinants, immunological tolerance reduces reactivity toward self. While this reduces the probability of autoimmunity, this also creates an important gap in adaptive immunity: the ability to respond to microbes that look like us. As a result, immunity against microbes that utilize molecular mimicry likely resides within the innate arm of immunity. Our initial studies demonstrate that a series of innate immune factors fill this important gap in adaptive immunity by specifically targeting microbes that decorate themselves in self-like antigen. These innate immune factors appear to specifically target these microbes by inducing loss of membrane integrity. Our studies seek to not only define the mechanisms whereby these innate immune factors impact microbial viability, but also determine the consequence of this form of innate immunity on anti-blood group antibody formation.
In addition, to examine the impact of microbial exposure on the development of naturally occurring antibodies against the ABO(H) blood group antigen system relevant in transfusion and transplantation, our lab studies the factors that contribute to the general immune response to carbohydrate antigens. As most carbohydrates do not appear to be processed and presented in a similar fashion as protein targets, we are identifying the unique factors that specifically impact the development of anti-carbohydrate antibody formation. Understanding these factors may not only provide a mechanism of inhibiting anti-carbohydrate antibody formation, such as anti-ABO(H) antibodies, but may also provide unique insight into the development of carbohydrate based vaccines against a wide variety of parasites.
Members of lab studying this area
Connie Arthur, Seema Patel, Anna Blenda, Nourine Kamili, Christian Gerner-Smidt, Jianmei Wang
- Stowell SR, Arthur CM, McBride R, Berger O, Razi N, Heimburg- Molinaro J, Rodrigues LC, Gourdine JP, Noll AJ, von Gunten S, Smith DF, Knirel YA, Paulson JC, Cummings RD. Microbial glycan microarray defines key features of host-microbial interactions. Nat Chem Biol 2014 Jun;10(6):470-6
- Stowell SR, Arthur CM, Dias-Baruffi M, Rodrigues LC, Gourdine JP, Heimburg-Molinaro J, Ju T, Molinaro RJ, Rivera-Marrero C, Xia B, Smith DF, Cummings RD. Innate immune lectins kill bacteria expressing blood group antigen. Nature Medicine 2010 Mar; 16(3):295-301
- Arthur CM, Patel SR, Mener A, Kamili NA, Fasano RM, Meyer E, Winkler AM, Sola-Visner M, Josephson CD and Stowell SR*. Innate Immunity against molecular mimicry: Examining galectin-mediated antimicrobial activity. Bioessays 2015 Dec; 37(12):1327-1337