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Role of sCD100 in in vitro and in vivo infection by different species of Leishmania

Grant number: 18/14972-8
Support type:Regular Research Grants
Duration: November 01, 2018 - May 31, 2021
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal researcher:Beatriz Simonsen Stolf
Grantee:Beatriz Simonsen Stolf
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Leishmaniasis is a zoonotic disease caused by protozoa of the genus Leishmania that may be classified in tegumentary (TL) or visceral (VL) forms. In humans and other vertebrate hosts, Leishmania preferentially infects macrophages. Many factors affect the form and severity of the disease, mainly the species of Leishmania and the host immune response. CD100 (Sema 4D) is a glycoprotein of the semaphoring family, which plays essential roles in the immune system. Our group showed that the soluble recombinant CD100 (sCD100) increases the infection of murine macrophages by Leishmania (Leishmania) amazonensis by interacting with CD72 receptor. We also showed increase in zymosan phagocytosis and in Trypanosoma cruzi infection. We believe similar increases in infection will be observed with other Leishmania species. Therefore, one of the aims of this project is to evaluate the effect of sCD100 on in vitro infection and in phagocytosis of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) chagasi, the species most commonly involved in TL and VL in Brazil, respectively. We will also investigate the effects of sCD100 on the infection of human macrophages. The mechanisms underlying the increase in infectivity of Leishmania will be determined by the proteomic analysis of proteins differentially expressed in macrophages treated with sCD100. The role of CD100 in vivo will be evaluated by comparing the infectivity of L. (L.) amazonensis in wild type mice and mice knockout for CD100. We believe that this study will help to elucidate the mechanisms by which CD100 increases the infectivity of Leishmania in macrophages and the role of this molecule in leishmaniasis. (AU)

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