Daniel Aldridge (Mentor: Christopher Hunter, PhD)

“IL-27 impacts emergency monopoiesis and monocyte function during acute Toxoplasma gondii infection”

Daniel L. Aldridge and Christopher A. Hunter

IL-27 is an immuno-modulatory cytokine composed of p28 and EBi3 subunits. During infection with the protozoan parasite Toxoplasma gondii, mice that lack IL-27 show dramatic alterations in their responses to infection, culminating in severe, infection-driven immunopathology. While this pathology is driven by aberrant CD4+ T cell responses at 7-10 days post-infection (dpi), the events that proceed, and contribute to, this response are unclear. 

We have recently observed that as early as 3dpi, substantial changes are apparent in the bone marrow of IL-27 deficient mice. IL-27 is produced in the bone marrow during infection, and the cells showing the highest expression of the receptor are hematopoietic stem-cells. Others have seen that IL-27 can function in emergency granulopoiesis during infectious setting, and so we investigated if IL-27 may play a similar function during toxoplasmosis. Intriguingly, in the absence of IL-27 T. gondii infected mice showed no difference in granulopoiesis but instead had a marked enhancement in monopoiesis. This difference was observed out to 5dpi, and, importantly, this enhancement in monopoiesis corresponded to an enhanced monocyte response in the periphery of infected mice. At the height of pathology, monocytes showed marked enhancement in their TNF⍺ and iNOS responses which may, in turn, contribute to the immunopathology in these mice. Thus, IL-27 appears to have a novel role in biasing cell fate and restraining the induction of a monocytic response during infection. Furthermore, it may have a previously unappreciated role in restraining HSCs from contributing to aberrant and pathological immune responses.