**1. Introduction**

Chagas' disease is a public health problem that affects about 6 to 7 million people worldwide, mainly who reside in the endemic areas of 21 countries of Latin America [1]. Despite the progress made to control the infection, the disease has been expanding to North America, Europe, Australia, and Japan by migration of million people from endemic countries [2–4]. The etiological agent of disease is the protozoan *Trypanosoma cruzi*, which shows a wide genetic variation, being classified in seven Discrete Typing Units (DTUs), TcI–TcVI, and Tcbat [5–7]. These different DTUs are

responsible for different disease outcomes, demonstrating the influence of parasite genetics on disease development [6]. Chagas' disease is classically transmitted by its insect vector, the triatomine bugs [8], but can also be acquired by blood transfusion [9, 10], congenitally [11, 12], by organ transplantation [13, 14], laboratory accidents [15], sexually [16], and by ingestion of contaminated food/juice [17]. After successful actions to interrupt vector transmission, oral contamination has been considered the main route of transmission in several countries [17–19]. Brazil is the country with the highest incidence of oral acute Chagas' disease outbreaks, mainly in the Amazon Basin ([19] reviewed by [20]). Oral acute Chagas' disease displays a higher number of signs and symptoms and higher lethality than those acquired through the vectorial route [17, 21].

In addition to parasite genetics and route of infection, disease outcome is also influenced by other factors such as evolutive forms of the parasite, parasite load, mixed infections [22–25], and host factors including immune response, concomitant infections, nutrition deficiencies, and host genetics [26]. Although several studies have tried to identify the genetic basis of Chagas disease, our knowledge on the subject is still vague. Many works have studied genetic polymorphisms located in genes associated with immune response [27] or over the whole genome [28, 29], but the influence of these polymorphisms on the pathology of the disease still needs to be further validated.

Considering the complexity of these factors and their influence in Chagas' disease immunopathogenesis, anti-*Trypanosoma cruzi* immune response and chemotherapy, there is a need to improve our understanding about these relationships. On this way, this study investigates the influence of the inoculation route and the host genetic background on the establishment and development of Chagas' disease in inbred and outbred mice, using an isolate of *T. cruzi* SC2005 strain (TcII) obtained from a human case from an oral Chagas' disease outbreak in the south region of Brazil [30]. The aim was to conduct a comparative analysis of the immunopathological, histopathological and hematological profiles, using parameters such as parasite load, survival rates, cytokines production, histopathology, and cell populations in the inflammatory sites.
