Role of sCD100 in macrophage in vitro infection by Leishmania (Viannia) braziliensis and Leishmania (Leishmania) chagasi and in in vivo infection by Leishmania (Leishmania) amazonensis

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. Some factors affect the form and severity of the disease, mainly the species of Leishmania inoculated by the insect vector and the host immune response. CD100 (Sema 4D) is a glycoprotein of the group of semaphorins, which play an essential role in the immune system. Our research group showed that the soluble recombinant CD100 (sCD100) increased the infectivity of Leishmania (Leishmania) amazonensis in murine macrophages by interacting with CD72 receptor. We here hypothesize that the same increase 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 parasite infectivity in vitro and rate of phagocytosis of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) chagasi, which are the species most commonly involved in TL and VL in Brazil, respectively. 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.