What we do
Understanding immune system biology through the study of chronic viral and parasitic infections.
Herpesviruses are viruses that establish lifelong chronic infections. During chronic infection, the virus is maintained in a latent state; however, it undergoes brief periods of reactivation. One of the lab's interests is how this balance between latency and reactivation is maintained by the host immune system.
During her postdoctoral work, Dr. Reese showed that parasite co-infection could induce herpesvirus reactivation. She demonstrated that the immune response to the parasite drove virus reactivation through the production of the cytokine interleukin-4 (IL-4). IL-4 signals directly to a viral promoter, activates the viral gene, and drives viral reactivation. In contrast, another cytokine, interferon (IFN)-gamma , through signaling to the same viral promoter, inhibits viral reactivation. These two host cytokines appear to counterbalance each other.
The Reese lab continues to study how co-infection and host-derived signals promote virus reactivation. We are investigating the relationship between the timing of parasite co-infection and viral reactivation and latency phenotypes. We are also studying differences in viral reactivation with altered microbial communities. Finally, we are determining the impact of activation of host nuclear receptors in herpesvirus reactivation.
How does chronic infection change the immune system’s ability to respond to secondary challenges?
The state of the immune system and its ability to respond to challenge is a function of many variables, which include genetics, age, chronic disease, gut microbiome, and stress. Recent work suggests that a significant proportion of the variation in human immune response is driven by non-heritable or environmental influences. Chronic infections with pathogens (including mycobacteria, helminths, malaria parasites, and some types of viruses) affect a large proportion of the population.
In addition to the diseases caused by these pathogens directly, it is increasingly clear that these persistent infections change immunity to other unrelated pathogens and to vaccines. While epidemiological and clinical data demonstrate an association between bystander chronic infections and altered immune responses there is little mechanistic data to explain these associations.
A more detailed understanding of the immune mechanisms could improve vaccine efficacy and treatment of chronic infections. Using chronic viral and helminth infections, we seek to further define the role of co-infections on vaccine responses in the mouse system.
Maternal Infection and Fetal Immune Programming
The crosstalk between mother and fetus significantly affects development of the fetal immune system. While we know that maternal diet, stress, smoking, microbiota, and even exposure to farm animals all influence neonatal immune development, we understand very little about the fundamental mechanisms that drive fetal immune programing. Recent associations of Zika virus infection in pregnant mothers to infant congenital abnormalities highlights the pressing need to understand the impact of maternal infections on fetal development. This need is even more apparent when one considers the hundreds of millions of mothers worldwide who harbor infections with helminths, malaria parasites, and HIV during pregnancy, all of which can alter immune responses without transmitting to the fetus. We aim to discover the relationship between maternal infection and altered fetal immune programming. We use our models of chronic infection, including Heligmosomoides polygyrus and murine gammaherpesvirus-68, to infect female mice prior to mating. Since neither of these pathogens transmit to the fetus, we can determine if the presence of maternal inflammation due to infection alters fetal immune programming. These studies will enhance our understanding of maternal-fetal interactions, but also have broad implications for efforts aimed at enhancing immunity in infants to vaccination or infection worldwide.