EFFECT OF BORRELIA BURGDORFERI ON THE STAT5 PATHWAY IN REGULATORY T CELLS

Abstract

Lyme disease, which is caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States. We have recently provided evidence that regulatory T (Treg) cells play a critical role in controlling the development of experimental Lyme arthritis. However, whether infection with B. burgdorferi affects Treg cells, themselves, has not been investigated. We hypothesized that B. burgdorferi activates the STAT5 pathway, leading to the development of Treg cells. We found that incubation of splenocytes with B. burgdorferi resulted in a significant increase in the proportion of Treg cells among total CD4+ T cells. In addition, we observed that among total CD4+ T cells, B. burgdorferi induced an increase in the proportion of Treg cells in which STAT5 was phosphorylated. These increases in cell proportions occurred in an antigen-dose-dependent manner. Furthermore, we observed a trend indicating that this effect may be dependent on IL-2, as neutralization of the cytokine decreased the proportion of these cells. Moreover, we did not observe these effects in conventional T cells. Collectively, our findings provide evidence that B. burgdorferi may induce the proportion of total, and activated, Treg cells in an IL-2 dependent manner. Our findings suggest a mechanism by which B. burgdorferi may modulate the host response to its advantage, possibly leading to sustained infection in the host.