BJRP 011007

Impact of vector-derived components on the innate immune responses to Leishmania, a Brazilian-Swiss collaborative research project on a neglected infectious disease

Abstract

Leishmaniasis is a major vector-borne disease of serious public health importance. It is endemic in more than 88 countries, according to WHO, 12 million are people presently infected worldwide, and 350 million at risk of infection. No vaccine is currently available against this disease.

Protozoan parasites of the genus Leishmania are the causative agents of the disease. Parasites are transmitted to the mammalian hosts by the bite of phlebotomine sand flies. During this process, not only parasites but also sand fly salivary products are delivered to the host. Many studies have been performed to understand the mechanisms leading to the protection or exacerbation of the disease, however, relatively few studies have investigated the role of the sand fly-derived salivary compounds in these processes. The objective of this proposal is to investigate the influence of sand fly saliva on the development of the immune response to infection with Leishmania. To this end, we will focus on two sand fly species (Lutzomyia intermedia and Lutzomyia longipalpis) and Leishmania braziliensis, the major causative agent of cutaneous leishmaniasis, all of which are endemic in Brazil.

The global effect of salivary gland extracts of Lutzomyia intermedia and of Lutzomyia longipalpis will be analyzed and compared employing both human blood in vitro systems and in vivo experimental models of Leishmania infection, using the combined expertises of the Brazilian and Swiss laboratories. Our hypothesis is that the early blood lake formed during sand fly feeding influences the behaviour and development of other neighbouring cells in a complex interplay. Results from the proposed study will be relevant in understanding the basic mechanisms involved in host immunity and the importance of sand fly components in this process with potential relevance in the design of vaccines.

Prof. F. TACCHINI-COTTIER

Dr A. P. BARRAL