IL-27 AND THE REGULATION OF INNATE AND ADAPTIVE IMMUNITY DURING TOXOPLASMOSIS

The cytokine IL-27 is a potent negative regulator of the inflammatory response to the pathogen Toxoplasma gondii, and the majority of the studies on IL-27 during this infection have focused on its ability to limit T cell responses. The basis for this suppressive activity is unclear, but it was proposed that the ability of IL-27 to promote T cell expression of inhibitory receptors (such as TIGIT and PD-L1) contributed to this activity. In chapter 2, the role of TIGIT during infection was assessed and indicated it was not a critical mediator of the suppressive effects of IL-27. In chapter 3, the impact of IL-27 neutralization on acute and chronic infection was examined and these data sets highlighted that in the absence of IL-27 there were enhanced monocyte responses, a cell type that does not express the IL-27R. During the later phase of infection, the overactive CD4+ T cell responses observed in the absence of IL-27 contributed to the increased monocyte response. However, analysis in chapter 4 of the most proximal events during infection-induced emergency myelopoiesis revealed that haemopoietic stem cells in the bone marrow express high levels of the IL-27R and that during infection IL-27 is a negative regulator of their differentiation into monocytes. Additionally, these studies revealed that IL-27 protected these stem cells from infection induced exhaustion. Thus, these studies highlight that IL-27 acts at multiple points during infection to limit key innate and adaptive events that contribute to infection-induced pathology.

Author dc:creator

• Aldridge, Daniel

Advisor dc:contributor.advisor

• Hunter, Christopher

• Immunology and Infectious Disease

Language dc:language.iso

en

Repository record dc:identifier.uri

https://repository.upenn.edu/handle/20.500.14332/61246

OAI identifier oai:identifier

oai:repository.upenn.edu:20.500.14332/61246