Student elective for Edward Prior. (360G-Wellcome-080975_Z_06_A)

Despite effective therapeutics and detection strategies, the prevalence and incidence of leprosy is still a public health concern across parts of Africa, Asia and South America. There is also much that remains unknown about its transmission and pathophysiology. Importantly it is not yet understood why some people are able to contain the infection and remain healthy whereas others succumb to the disease because they are unable to mount an effective immune response. The host response to this disease ranges along an immunological spectrum. T helper cell type 1 leprosy responses, distinguished by IFNg expressin, result in paucibacillary (tuberculoid) leprosy where bacteria re contained and destroyed. Multibacillary (lepromatous) leprosy is characterised by Th2 cells expressing IL4 which are unstable and can switch from protective to susceptible depending on the immunological status of the host. Leprosy is caused by Mycobacterium leprae. It infects primarily Schwann cells and macrophages. Host responses to infection involve the formation of granulomata, an attempt by the host to contain and destroy the bacteria. Those with tuberculoid leprosy mount an effective cell mediated immune response with T cell activated macrophages killing the bacteria. There is an absence of an effective T cell response in lepromatous granulomata and macrophages are unable to kill their bacterial load. However, in an attempt to control infection there is further macrophage recruitment. It is the role of these fresh cells that my host laboratory are currently investigating as part of their efforts to establish an in vitro granuloma model. Work published by Dr Adams' laboratory has shown, in mice, that activation of freshly recruited macrophages is able to reduce the viability of M. leprae even in the absence of T cells. During my elective period we would like to further investigate the role of human macrophages using an in vitro model.