Mechanisms Of Leishmania Uptake And Transmission By Phlebotomine Sand Flies (diptera: Psychodidae

Abstract

Leishmania parasites undergo cyclical development in their vector sand fly through various stages before they can be transmitted by bite. Sand fly saliva aids in blood-feeding by modulating host-immune responses through processes such as prevention of clotting. Sand fly saliva also promotes the invasion and intracellular survival of Leishmania in potentially lethal macrophages by suppressing macrophage activation and antigen presenting functions. Sand fly saliva-mediated immunomodulation, together with suppression of the expression of cell surface antigens and phagocytic functions of macro phages ensure successful parasitization of a susceptible host by the Leishmania parasite. To further investigate the role of sand fly saliva in the establishment and uptake of Leishmania parasites, various experiments were designed to test: (1) the effect of co- inoculation of Phlebotomus duboscqi salivary gland lysates with Leishmania major promasttgotes on lesion development in BALB/c mice, (ii) to determine the sequence of inflammatory reactions of hamster. skins after needle inoculation with P. duboscqi salivary gland lysates and after .bites of uninfected and L. major-infected P. duboscqi, (iii) to determine whether P. duboscqi saliva is chemotactic to macrophages and its effect on host complement, and lastly, (iv) to determine whether sand fly saliva influences the course of viscerotropic L. donovanL Results obtained from this study showed that saliva of P. duboscqi enhances the infectivity of L. major. Intradermal inoculation of sand fly saliva either by needle or bites of uninfected or L. majorinfected P. duboscqi, generated an inflammatory reaction that was initially characterised by vascular congestion, neutrophilia and mixed cell infiltrate, and in 48-96 hours the macrophage became the predominant cell type, suggesting that saliva is chemotactic to macro phages in vivo. In vitro, sand fly saliva was shown to be chemotactic to mouse peritoneal macrophages, a factor that may ensure successful parasitization of a host, and partially explain how post kala-azar dermal letshmantasts develops, and also how Leishmania amasttgotes are taken up by the sand fly. The sequence of inflammatory reactions was studied using standard histological tissue sectioning and staining with toluidine blue, haematoxylin and eosin, and light microscopy. It was demonstrated that P. duboscqt. saliva does not prevenf lysts of sheep erythrocytes by guinea pig complement. This may also contribute to successful parasitization of a host. Despite the fact that P. duboscqi saliva was shown to enhance infectivity of L. major, it was demonstrated that it does not influence the course and subsequent uptake of viscerotropic L. donouoni: This study has demonstrated that like saliva of Lu. longipalpis and P. papatasi, saliva of P. duboscqi contains maxadilan, the Leis hmania enhancing factor that exacerbates infectivity of L. major.