Conferencia Dra. Traub-Cseko

Unraveling the molecular interactions between Leishmania and sandflies. And going beyond.

Vinicius Wakoff Fonseca¹, Nathalia Batista¹, Thais Lemos-Silva¹, David L. Sacks², Antonio Tempone¹, Yara Maria Traub-Cseko¹

¹Laboratório de Biologia Molecular de Parasitas e Vetores, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro – RJ – Brasil
²Department of Laboratory Medicine, National Institutes of Health, Bethesda – US
E-mail address: ytraub@ioc.fiocruz.br 

Leishmaniasis is considered a major neglected public health problem and there has been a significant increase in the number of human cases in recent years. There is a demand for new approaches in the control of leishmaniasis due to the lack of vaccines and limitations in the use of traditional vector control methods, such as insecticide resistance, costs, etc. A good knowledge of the mechanisms involved in parasite-vector interactions can lead us to the development of such techniques. Our laboratory is working on various aspects of the molecular interactions between Leishmania and sandfly, mostly the Lutzomyia longipalpis– Leishmania infantum chagasi pair, responsible for visceral leihsmaniasis transmission in South America. We have uncovered various insect immune responses when infected with the parasite, that go from the production of antimicrobial peptides to the activation of specific immune pathways. We also detected responses that are reminiscent of the vertebrate host immune responses, showing an interesting evolutionary conservation between mammals and vectors. We used two populations of Nyssomyia umbratilis, vector of American tegumentary leishmaniasis (ATL) in the Amazon, with a striking difference in vectorial capacity, to investigate possible molecules responsible for this competence. We performed proteomics and microbiota metagenomics analyses that revealed differences in microbiota and proteins related to immunity and gut function, among others. In possession of all this information we are presently testing putative candidates for the development of transmission-blocking vaccines (TBVs), which consist on the immunization of the mammalian hosts with vector or parasite antigens responsible for establishing the pathogen in the vector, thus stimulating the production of neutralizing antibodies that will interrupt the development of the parasite inside the vector, thus blocking transmission upon a new infected bloodmeal acquisition by the vector. We are identifying several promising candidates in the parasite, both by testing vector infection with mutant parasites (either obtained through collaborations or by creating mutants through CRISPR) and performing artificial infections in the presence of antibodies against proteins of interest. Among these are proteins related to iron metabolism, amino acids transporters and a Leishmania chitinase. A mutant for this chitinase obtained by CRISPR was 100 times less efficient than control insects in artificial transmission assays. Immune sera obtained against these target proteins were used in artificial infections of L. longipalpis with L. i. chagasi showing promising results with significant decrease of parasite load in insects infected in the presence of these sera.

Keywords: Leishmaniasis, Vector-parasite interaction, Transmission blocking vaccines.