Developing host directed therapies to treat inflammatory diseases
Speaker: Christian Engwerda, Group Leader, QIMR Berghofer, Brisbane, Australia
The human immune system has evolved to combat infections, while maintaining functional tissues and a healthy microbiome. This requires rapid activation and expansion of immune cells that recognise and kill pathogens, but also needs the establishment of regulatory mechanisms that control associated inflammation. Chronic infectious diseases such as visceral leishmaniasis (VL) and malaria are characterised by the breakdown of these regulatory networks, resulting in uncontrolled inflammation that causes disease. We recently isolated peripheral blood CD4+ T cells from VL patients and endemic controls, isolated RNA and performed RNAseq. We identified differentially expressed genes between VL patient and endemic controls, and identified type I interferon (IFN) signalling as a major upstream regulator of CD4+ T cell functions. Here, I will present follow-up studies to investigate the effects of type I IFNs on CD4+ T cell function and disease outcome during VL and malaria. In addition, I will describe the discovery of a novel therapeutic target from our RNAseq data set that is expressed on a broad range of immune cells with functions in a diverse array of inflammatory diseases.