Ascaris lumbricoides Cystatin Prevents Development of Allergic Airway Inflammation in a Mouse Model

Front Immunol. 2019 Sep 27;10:2280. doi: 10.3389/fimmu.2019.02280. eCollection 2019.

Abstract

Severe helminth infections are negatively associated to allergic diseases like asthma; therefore, the immunomodulatory properties of parasite-derived components have been analyzed, raising the possibility of their use as anti-inflammatory molecules. We evaluated the immunomodulatory properties of Ascaris lumbricoides recombinant cysteine protease inhibitor (rAl-CPI) in a mouse model of allergic airway inflammation induced by the house dust mite (HDM) Blomia tropicalis and its effects on human monocyte-derived dendritic cells (HmoDCs). The B. tropicalis sensitized/challenged mice developed extensive cellular airway inflammatory response, which was significantly reduced upon treatment with rAl-CPI prior to B. tropicalis sensitization, affecting particularly the perivascular/peribronchial infiltrate cells, eosinophils/neutrophils, and goblet cells. A significant decrease of Th2 cytokines, total, and specific IgE antibodies was observed in rAl-CPI treated mice. The antibody response was biased to IgG, mainly IgG2a. Administration of rAl-CPI-alone and rAl-CPI before mite sensitization were associated with a significant increase of regulatory T cells (Tregs) in spleen and elevated IL-10 levels in BAL and splenocytes culture supernatants, which was partially affected by anti-IL10 receptor use. In vitro, rAl-CPI showed a modulatory effect on HmoDCs, lowering the expression of HLA-DR, CD83, and CD86, while inducing IL-10 and IL-6 production. This suggests an inhibition of HmoDC maturation and a possible link with the inhibition of the allergic response observed in the murine model.

Keywords: Ascaris; IL-10; IgE; Tregs; allergy; dendritic cells; immunomodulation; recombinant cystatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology
  • Animals
  • Ascaris lumbricoides / immunology*
  • Asthma / immunology
  • Cystatins / immunology*
  • Cytokines / immunology
  • Dendritic Cells / immunology
  • Disease Models, Animal
  • Eosinophils / immunology
  • Female
  • Humans
  • Hypersensitivity / immunology*
  • Immunoglobulin G / immunology
  • Inflammation / immunology*
  • Interleukin-10 / immunology
  • Mice
  • Mice, Inbred BALB C
  • Neutrophils / immunology
  • Pyroglyphidae / immunology
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Allergens
  • Cystatins
  • Cytokines
  • Immunoglobulin G
  • Interleukin-10