MicroRNA-155 Deficiency Exacerbates Trypanosoma cruzi Infection

Infect Immun. 2020 Jun 22;88(7):e00948-19. doi: 10.1128/IAI.00948-19. Print 2020 Jun 22.

Abstract

Chagas disease, caused by the intracellular protozoan parasite Trypanosoma cruzi, is a public health problem affecting 6 to 8 million people, mainly in Latin America. The role of microRNAs in the pathogenesis of Chagas disease has not been well described. Here, we investigate the role of microRNA-155 (miR-155), a proinflammatory host innate immune regulator responsible for T helper type 1 and type 17 (Th1 and Th17) development and macrophage responses during T. cruzi infection. For this, we compared the survival and parasite growth and distribution in miR-155-/- and wild-type (WT) C57BL/6 mice. The lack of miR-155 caused robust parasite infection and diminished survival of infected mice, while WT mice were resistant to infection. Immunological analysis of infected mice indicated that, in the absence of miR-155, there was decreased interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) production. In addition, we found that there was a significant reduction of CD8-positive (CD8+) T cells, natural killer (NK) cells, and NK-T cells and increased accumulation of neutrophils and inflammatory monocytes in miR-155-/- mice. Collectively, these data indicate that miR-155 is an important immune regulatory molecule critical for the control of T. cruzi infection.

Keywords: Chagas disease; Trypanosoma cruzi; immune response; miR-155; microRNA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chagas Disease / genetics*
  • Chagas Disease / immunology
  • Chagas Disease / mortality
  • Chagas Disease / parasitology*
  • Cytokines / metabolism
  • Disease Progression
  • Disease Susceptibility / immunology
  • Genetic Predisposition to Disease
  • Kaplan-Meier Estimate
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / genetics*
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Prognosis
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Trypanosoma cruzi* / immunology

Substances

  • Cytokines
  • MicroRNAs
  • Mirn155 microRNA, mouse