title: The Driving of Immune Response by Th1 Adjuvants in Immunization of Mice with Trypanosoma cruzi marinkellei Elicits a Controversial Infection Control.
abstract: In previous studies, we have demonstrated that inoculation with a Trypanosoma cruzi marinkellei (avirulent RM1 strain) was able to reduce parasitemia in mice challenged with T. cruzi, although it was not able to prevent histopathological lesions. Th1 response stimulation by immunization is necessary for T. cruzi infection control, but the resistance is also dependent on immunoregulatory mechanisms, which can be induced by adjuvants. Thus, we evaluated whether inoculation of T. cruzi marinkellei associated with administration of different adjuvants would be capable of inducing different patterns of immune response to maximize the immune response against T. cruzi (virulent Romildo strain) infection. Two hundred eighty nonisogenic mice were divided into 14 groups according to the immunization scheme and the subsequent challenge with virulent Romildo T. cruzi strain. Nonimmunized groups and animals inoculated without adjuvants were also included. Immune protection was not observed with Th2 adjuvants (incomplete Freund's adjuvant [IFA] and Alum) due to high parasitemia. Th1/Th2-polarizing adjuvants also did not induce immune protection because inulin was unable to maintain survival, and immune-stimulating complexes induced intense inflammatory processes. Animals sensitized with RM1 strain without adjuvants were able to reduce parasitemia, increase survival, and protect against severe histological lesions, followed by adequate cytokine stimulation. Finally, our results demonstrate that the early and balanced IFN-γ production becomes critical to promote protection and that Th1 adjuvant elicited a controversial infection control due to increased histopathological damage. Therefore, the host's immunomodulation remains one of the most important challenges in the research for effective protection against T. cruzi infection. Similarly, the identification of protective antigens in the RM1 strain of T. cruzi marinkellei may contribute to further studies on vaccine development against human Chagas disease.
authors.affiliation: 1 Microbiology and Immunology Discipline, Federal Institute of Education , Science and Technology at Triângulo Mineiro (IFTM), Uberaba, Brazil .
authors.forename: Gabriel Antonio Nogueira
authors.initials: GA
authors.lastname: Nascentes
authors.affiliation: 2 Department of Microbiology, Immunology and Parasitology, Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro (UFTM) , Uberaba, Brazil .
authors.forename: César Gómez
authors.initials: CG
authors.lastname: Hernández
authors.affiliation: 2 Department of Microbiology, Immunology and Parasitology, Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro (UFTM) , Uberaba, Brazil .
authors.forename: Rosiley Aparecida de Souza
authors.initials: RA
authors.lastname: Rabelo
authors.affiliation: 2 Department of Microbiology, Immunology and Parasitology, Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro (UFTM) , Uberaba, Brazil .
authors.forename: Raquel Fernandes
authors.initials: RF
authors.lastname: Coelho
authors.affiliation: 3 School of Pharmaceutical Sciences at Ribeirão Preto, University of São Paulo (USP) , Ribeirão Preto, Brazil .
authors.forename: Fabiana Rossetto de
authors.initials: FR
authors.lastname: Morais
authors.affiliation: 2 Department of Microbiology, Immunology and Parasitology, Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro (UFTM) , Uberaba, Brazil .
authors.forename: Tatiane
authors.initials: T
authors.lastname: Marques
authors.affiliation: 2 Department of Microbiology, Immunology and Parasitology, Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro (UFTM) , Uberaba, Brazil .
authors.forename: Lara Rocha
authors.initials: LR
authors.lastname: Batista
authors.affiliation: 2 Department of Microbiology, Immunology and Parasitology, Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro (UFTM) , Uberaba, Brazil .
authors.forename: Wendell Sérgio Ferreira
authors.initials: WS
authors.lastname: Meira
authors.affiliation: 2 Department of Microbiology, Immunology and Parasitology, Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro (UFTM) , Uberaba, Brazil .
authors.forename: Carlo José Freire de
authors.initials: CJ
authors.lastname: Oliveira
authors.affiliation: 2 Department of Microbiology, Immunology and Parasitology, Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro (UFTM) , Uberaba, Brazil .
authors.forename: Eliane
authors.initials: E
authors.lastname: Lages Silva
authors.affiliation: 2 Department of Microbiology, Immunology and Parasitology, Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro (UFTM) , Uberaba, Brazil .
authors.forename: Luis Eduardo
authors.initials: LE
authors.lastname: Ramírez
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D014355:Chagas Disease / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051379:Mice; D016052:Protozoan Vaccines / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000145:classification / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D016052:Protozoan Vaccines
keywords: Adjuvant; Cytokine; IFN-γ; Immunization; Trypanosoma cruzi marinkellei