Identification of the First Direct Interaction between

Trypanosomes and the Host Immune System

Olivia Macleod

African sleeping sickness

Endemic to sub-Saharan Africa

Caused by the parasite Trypanosoma brucei

Transmitted by the tsetse fly

Lives in the bloodstream of humans and livestock

Ineffective treatments

Photos: Brun et al. (2010); Prof. Michael Duszenko, Universität Tübingen

African sleeping sickness

Endemic to sub-Saharan Africa

Caused by the parasite Trypanosoma brucei

Transmitted by the tsetse fly

Lives in the bloodstream of humans and livestock

Ineffective treatments

Photos: Brun et al. (2010); Prof. Michael Duszenko, Universität Tübingen

How does the parasite avoid detection in our bloodstream and

destruction by our immune systems?

Avoiding the immune system

Immune attack 1 Immune attack 2

Grey destroyedYellow survive and multiply

Yellow destroyedRed survive and multiply

Process continues for many

years

The parasites constantly change their surface coat

How, then, can we target these parasites?

Close-up of parasite surface

Parasite surface: a weak spot

Known surface proteins that take

up essential nutrients from the

bloodstream

Unknown surface proteins

Known surface proteins that take

up essential nutrients from the

bloodstream

Unknown surface proteins

Close-up of parasite surface

Parasite surface: a weak spot

Aim of PhD

To determine the function of these surface proteins in order to obtain a complete understanding of the molecular interaction between the parasite and the host

Identifying novel surface proteins

Human and cattle bloodstream Tsetse fly

Factor H

Importance of discovery

Factor H-binding protein is the first discovery of a direct interaction between the host immune system and this parasite

Blocking the interaction between Factor H and the parasite may prevent its survival in the host

Two additional surface proteins have been discovered that bind components in the bloodstream

Factor H

Commercial application

Progress with company in Cambridge

Producing monoclonal antibodies against two trypanosome surface proteins

Could lead to a targeted treatment against African sleeping sickness

Commercial application

Progress with company in Cambridge

Monoclonal antibody competes/interferes with Factor H binding

Parasite death

Factor H

AcknowledgementsCarrington Lab Members Lab Funding PhD Funding

Magdalene CollegeUniversity of Cambridge

Cambridge Society for the Application of Research