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Induction of Effective Immunity against Trypanosoma cruzi.
Williams, Tere; Guerrero-Ros, Ignacio; Ma, Yanfen; Matos Dos Santos, Fabiane; Scherer, Philipp E; Gordillo, Ruth; Horta, Aline; Macian, Fernando; Weiss, Louis M; Huang, Huan.
Afiliación
  • Williams T; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
  • Guerrero-Ros I; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
  • Ma Y; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
  • Matos Dos Santos F; Department of Pharmacy and Nutrition, Federal University of Espírito Santo, Guararema, Alegre, ES, Brazil.
  • Scherer PE; The Touchstone Diabetes Center, UT Southwestern Medical Center, Dallas, Texas, USA.
  • Gordillo R; The Touchstone Diabetes Center, UT Southwestern Medical Center, Dallas, Texas, USA.
  • Horta A; Universidade Federal de Ouro Preto CBIOL, Ouro Preto, MG, Brazil.
  • Macian F; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
  • Weiss LM; Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
  • Huang H; Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
Infect Immun ; 88(4)2020 03 23.
Article en En | MEDLINE | ID: mdl-31907197
Chagas disease, caused by Trypanosoma cruzi, is a major public health issue. Limitations in immune responses to natural T. cruzi infection usually result in parasite persistence with significant complications. A safe, effective, and reliable vaccine would reduce the threat of T. cruzi infections; however, no suitable vaccine is currently available due to a lack of understanding of the requirements for induction of fully protective immunity. We established a T. cruzi strain expressing green fluorescent protein (GFP) under the control of dihydrofolate reductase degradation domain (DDD) with a hemagglutinin (HA) tag, GFP-DDDHA, which was induced by trimethoprim-lactate (TMP-lactate), which results in the death of intracellular parasites. This attenuated strain induces very strong protection against reinfection. Using this GFP-DDDHA strain, we investigated the mechanisms underlying the protective immune response in mice. Immunization with this strain led to a response that included high levels of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α), as well as a rapid expansion of effector and memory T cells in the spleen. More CD8+ T cells differentiate to memory cells following GFP-DDDHA infection than after infection with a wild-type (WT) strain. The GFP-DDDHA strain also provides cross-protection against another T. cruzi isolate. IFN-γ is important in mediating the protection, as IFN-γ knockout (KO) mice failed to acquire protection when infected with the GFP-DDDHA strain. Immune cells demonstrated earlier and stronger protective responses in immunized mice after reinfection with T. cruzi than those in naive mice. Adoptive transfers with several types of immune cells or with serum revealed that several branches of the immune system mediated protection. A combination of serum and natural killer cells provided the most effective protection against infection in these transfer experiments.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trypanosoma cruzi / Subgrupos de Linfocitos T / Vacunas Antiprotozoos / Enfermedad de Chagas Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Infect Immun Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trypanosoma cruzi / Subgrupos de Linfocitos T / Vacunas Antiprotozoos / Enfermedad de Chagas Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Infect Immun Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos