Host defence to Toxoplasma gondii
The protozoan parasite Toxoplasma gondii infects a broad range of hosts, with a seroprevalence in man of about 30 per cent. It is unclear how Toxoplasma maintains the intricate balance between survival and host defense.
IFNγ, the main cytokine responsible for its control, activates cells to restrict intracellular parasite replication or to kill intracellular Toxoplasma. Cell-mediated immunity, driven mostly by CD8 T cells, confers resistance to the chronic phase of the parasite. The outcome of an infection with Toxoplasma is determined not only by the host’s immune status, but also by the genotype of the infecting strain. The major cause of Toxoplasma pathogenesis results from parasite burden, concurrent with an over-stimulation of the immune system in the form of high levels of T helper cell type 1 cytokines, increased apoptosis and organ damage.
Our long-term goal is to identify IFNγ-driven novel pathways of host resistance to Toxoplasma in human cells. We are studying how the parasitophorous vacuole (PV) is remodeled within host cells to limit parasite replication. Additionally, we are interested in IFNγ-dependent immune defence mechanisms that in general can limit Toxoplasma viability. The pathways we study often also impact bacterial or other eukaryotic pathogens as well as Toxoplasma. Therefore, the Frickel lab strives to uncover human IFNγ-dependent host defence pathways of broad relevance to eukaryotic and bacterial pathogens.
Host Response to Microbe Analysis: Artificial intelligence-driven image analysis
We developed HRMAn as an intelligent, image-based analysis program that allows for unbiased, quantitative assessment of host-pathogen interactions. HRMAn is a high-performance, user-friendly analysis pipeline designed in KNIME. HRMAn can run on any computer, analyse images from any fluorescent microscope and cater to a wide-range of pathogens without any need for additional coding by the users. The core of HRMAn is its unprecedented neural network-driven analysis of host protein recruitment to pathogens.
We are open to collaboration to develp HRMAn for other pathogens.
Further detail on the HRMAn website: HRMAn (Host Response to Microbe Analysis)
The Frickel Lab is at The Francis Crick Institute.