**1. Introduction**

Chagas disease, despite the success of public policies for vector control, still has a worrying annual incidence in Brazil, especially in the precarious and growing

frontiers of the legal Amazon [1]. The etiologic agent of Chagas' disease is the protozoan *Trypanosoma cruzi*, transmitted through the bites of insects of the Triatominae subfamily, in blood transfusions, or orally through the ingestion of contaminated food with the waste of vector insects [2]. The incidence of the disease through classical transmission by triatomines cohabiting human residences has been significantly reduced as a result of the effectiveness of public vector control and housing improvement programs [3]. However, there is a growing number of cases in the states of the Legal Amazon, where there are wild triatomines that, as they do not invade human dwellings, cannot be easily controlled by traditional containment measures [4]. The frequent result is oral contamination through ingestion of products contaminated by vectors infected with *Trypanosoma cruzi*, such as açaí pulp [5], in addition to the expansion of vector transmission by wild triatomines, whose incidence only should grow as deforestation continues in the region [6]: between 2000 and 2016, more than 2000 confirmed acute cases in Belém in the State of Pará, Brazil, Amazon region [7].

*T. cruzi* belongs to the order Trypanosomatida, which also harbors the genus *Leishmania*, another widely distributed human parasite that causes leishmaniasis, also, an important neglected disease. Genetic analysis of members of this order revealed the presence of genes that encode serine peptidase inhibitors (ISPs), in the genera *Leishmania* and *Trypanosoma.* The ISPs observed in these trypanosomatids are orthologs of ecotin, an inhibitor found only in gram-negative bacteria [8], suggesting a possible lateral genetic transfer at some point in the evolution of these taxa. This fact, quite interesting in itself, becomes more intriguing when we consider that the sequencing did not reveal the presence, in the genome of the studied parasites, of serine peptidases of the types that ecotin inhibits, as it indicates that trypanosomatid ISPs have exogenous targets [9].

In bacteria, especially those that invade arthropod and vertebrate tissue, a growing variety of studies indicates that ecotin is a key factor in defense against the immunological barriers of infected organisms. Recent evidence indicates that ISPs synthesized by *Leishmania major*, which are also ecotin orthologs, have an exogenous function, facilitating the parasite's survival against the host immune system. Drawing a parallel between studies with ecotin-bearing bacteria and ISPs of *L. major* —a parasite that belongs to a sister group of *T. cruzi*—it is clear the fundamental role that these serine peptidase inhibitor proteins play in modulating the immune response of these parasite hosts. Next, we compared the position of ecotin in various members of the Kinetoplastida group to reinforce the hypothesis of its possible common origin from horizontal transfer. Besides, the interaction of ISP2 from *T. cruzi* (TcISP2) with the vertebrate host immune system will be demonstrated by its antigenicity property in the murine model of Chagas' disease.
