Authors
N Mabbott1; 1 The Roslin Institute, UK Discussion
African trypanosomes are single-celled extracellular protozoan parasites transmitted by tsetse fly vectors across sub-Saharan Africa, causing serious disease in both humans and animals. Natural mammalian infections begin when an infected tsetse fly penetrates the skin in order to take a blood meal, depositing trypanosomes into the dermis. Similarly, onward transmission occurs when differentiated and insect pre-adapted parasite forms are ingested by the fly during a blood meal. Between these transmission steps, trypanosomes access the systemic circulation of the vertebrate host via the skin-draining lymph nodes, disseminating into multiple tissues and organs, and establishing chronic, and long-lasting infections. However, most studies of the immunobiology of African trypanosomes have been conducted under experimental conditions that bypass the skin as a route for systemic dissemination (typically via intraperitoneal or intravenous routes). Therefore, the importance of these initial interactions between trypanosomes and the skin at the site of initial infection, and the implications for these processes in infection establishment, are often overlooked. I will discuss mechanisms involved in establishing African trypanosome infections via the skin, especially the role of innate immune cells in the skin and the local draining lymph nodes. I will also discuss data from studies of the subsequent immune interactions as the parasites migrate from the skin and the pathological consequences as they eventually establish infection in the central nervous system. The many studies of experimental systemic African trypanosome infections have of course helped to uncover important interactions between the parasite and the mammalian host’s immune system. However, a thorough identification of the mechanisms involved in establishing African trypanosome infections in the skin and their subsequent progression through the host is essential for the development of novel approaches to block disease transmission. 
