Evaluation of pathogen P21 protein as a potential modulator of the protective immunity induced by Trypanosoma cruzi attenuated parasites

Mem Inst Oswaldo Cruz. 2019:114:e180571. doi: 10.1590/0074-02760180571. Epub 2019 May 20.

Abstract

Background: TcP21 is a ubiquitous secreted protein of Trypanosoma cruzi and its recombinant form (rP21) promotes parasite cell invasion and acts as a phagocytosis inducer by activating actin polymerisation in the host cell.

Objective: Our goal was to evaluate if the additional supplementation of rP21 during a prime/boost/challenge scheme with T. cruzi TCC attenuated parasites could modify the well-known protective behavior conferred by these parasites.

Methods: The humoral immune response was evaluated through the assessment of total anti-T. cruzi antibodies as well as IgG subtypes. IFN-γ, TNF-α and IL-10 were measured in supernatants of splenic cells stimulated with total parasite homogenate or rP21.

Findings: Our results demonstrated that, when comparing TCC+rP21 vs. TCC vaccinated animals, the levels of IFN-γ were significantly higher in the former group, while the levels of IL-10 and TNF-α were significantly lower. Further, the measurement of parasite load after lethal challenge showed an exacerbated infection and parasite load in heart and skeletal muscle after pre-treatment with rP21, suggesting the important role of this protein during parasite natural invasion process.

Main conclusion: Our results demonstrated that rP21 may have adjuvant capacity able to modify the cytokine immune profile elicited by attenuated parasites.

MeSH terms

  • Animals
  • Antibodies, Protozoan / immunology*
  • Antigens, Protozoan / immunology*
  • Chagas Disease / immunology*
  • Chagas Disease / prevention & control
  • Disease Models, Animal
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Interferon-alpha / blood
  • Interferon-alpha / immunology
  • Interferon-gamma / blood
  • Interferon-gamma / immunology
  • Interleukin-10 / blood
  • Interleukin-10 / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phagocytosis
  • Protozoan Proteins / immunology*
  • Trypanosoma cruzi / immunology*
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / immunology*

Substances

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Immunoglobulin G
  • Interferon-alpha
  • Protozoan Proteins
  • Vaccines, Attenuated
  • Interleukin-10
  • Interferon-gamma