Juselyn Tupik

Brucella abortus is Recognized by the Inflammasome and Negative Regulator NLRX1 of the Innate Immune System

Biomedical and Veterinary Sciences |

Virginia Tech-Maryland College of Veterinary Medicine

Co-Authors: C. Caswell, S. Coutermash-Ott, A. Hollis Benton, K. King

Advisor: Irving Coy Allen

Abstract

Brucella abortus, a bacteria that causes the zoonotic disease brucellosis, is relatively understudied in the context of innate immune system recognition. Pattern recognition receptors (PRRs) play a key role in this system by recognizing pathogens and promoting the expression of cytokines to inhibit or promote an immune response. One such PRR is NLRX1 (NLR family), a negative modulator of innate immunity that inhibits the expression of proinflammatory cytokines. In contrast, the adaptor protein ASC promotes inflammation by complexing with many PRRs to form the inflammasome, which acts as a central signaling hub. The activation of both NLRX1 and ASC in response to a B. abortus has not been previously determined. Therefore, we used macrophages from wild type, Nlrx1-/-, and Asc-/ - mice to elucidate the RNA expression and protein secretion of proinflammatory cytokines in response to B. abortus infection. Additionally, in vivo infections in Asc-/- mice were conducted to determine the mortality rates and protein expression of proinflammatory cytokines. We found that Nlrx-/- macrophages exhibited increased expression of proinflammatory cytokines, while Asc-/- exhibited decreased expression and secretion. Asc-/- mice also showed higher mortality and decreased proinflammatory signaling in the liver and spleen than wild type mice. This may indicate that B. abortus interacts with both the inflammasome and NLR PRRs in the innate immune system. Further studies determining the immune recognition of B. abortus are essential for the development of effective brucellosis treatments.

Bio

Juselyn Tupik is a first-year D.V.M./Ph.D. student in the Biomedical & Veterinary Sciences Department at the VA-MD College of Veterinary Medicine at Virginia Tech. She is investigating how infectious diseases are recognized and targeted by the innate immune system. She obtained her B.S. in Biology from William & Mary in 2019.

Tupik, Juselyn.pdf