38th Annual Meeting of the Society for Invertebrate Pathology

August 7-11, 2005  Anchorage, Alaska, U.S.A
   

Sand fly midgut receptors for Leishmania parasites: targets for transmission-blocking vaccines

Shaden Kamhawi2, Marcelo Ramalho-Ortigao 1, Van M. Pham 1,Sanjeev Kumar 3 , Phillip G. Lawyer 2 , Salvatore J. Turco 4 , Carolina Barillas-Mury 3 , David L. Sacks 2, Jesus G. Valenzuela 1 .
1 Vector Molecular Biology Unit, Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Bethesda, MD, 20892, USA. 2 Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
3 Mosquito Immunity and Vector Competence Unit, Laboratory of Malaria and Vector Research, NIAID, NIH, MSC 8132, Bethesda, MD 20892-8132. 4 University of Kentucky Medical Center, Department of Molecular and Cellular Biochemistry, Lexington, Kentucky, 40502, USA

We have isolated from a P. papatasi sand fly midgut cDNA library a transcript coding for a galectin (PpGalec). The observed homology of PpGalec to galactose-binding proteins, together with previous studies indicating that poly-Gal (β1-3) side chains of Leishmania major lipophosphoglycan (LPG) are responsible for specific binding to P. papatasi midguts, suggested that PpGalec is the midgut receptor for L. major in this sand fly species. Expression of PpGalec in P. papatasi is upregulated in adult females and is restricted to midgut tissue; expression of PpGalec is restricted to P. papatasi and P. duboscqi sister species belonging to the subgenus Phlebotomus. The binding specificity of recombinant PpGalec is restricted to Leishmania promastigotes bearing poly-Gal (β1-3) side chains on their LPG. PpGalec is localized on the luminal surface of midgut cells. Interestingly, antibodies against PpGalec inhibited ex vivo midgut binding of L. major PG and parasites, additionally, PpGalec antibodies fed to P. papatasi severely impaired parasite development and survival in the insect midgut. This is the first molecular description of a parasite receptor in the midgut of its insect vector. In addition, these studies demonstrate the feasibility of using midgut receptors for parasite ligands as target antigens for transmission-blocking vaccines.

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