The Helminth-Derived Immunomodulator AvCystatin Reduces Virus Enhanced Inflammation by Induction of Regulatory IL-10+ T Cells

PLoS One. 2016 Aug 25;11(8):e0161885. doi: 10.1371/journal.pone.0161885. eCollection 2016.


Respiratory Syncytial Virus (RSV) is a major pathogen causing low respiratory tract disease (bronchiolitis), primarily in infants. Helminthic infections may alter host immune responses to both helminths and to unrelated immune triggers. For example, we have previously shown that filarial cystatin (AvCystatin/Av17) ameliorates allergic airway inflammation. However, helminthic immunomodulators have so far not been tested in virus-induced disease. We now report that AvCystatin prevents Th2-based immunopathology in vaccine-enhanced RSV lung inflammation, a murine model for bronchiolitis. AvCystatin ablated eosinophil influx, reducing both weight loss and neutrophil recruitment without impairing anti-viral immune responses. AvCystatin also protected mice from excessive inflammation following primary RSV infection, significantly reducing neutrophil influx and cytokine production in the airways. Interestingly, we found that AvCystatin induced an influx of CD4+ FoxP3+ interleukin-10-producing T cells in the airway and lungs, correlating with immunoprotection, and the corresponding cells could also be induced by adoptive transfer of AvCystatin-primed F4/80+ macrophages. Thus, AvCystatin ameliorates enhanced RSV pathology without increasing susceptibility to, or persistence of, viral infection and warrants further investigation as a possible therapy for virus-induced airway disease.

MeSH terms

  • Animals
  • Bronchiolitis / complications
  • Bronchiolitis / immunology
  • Bronchiolitis / prevention & control
  • Cell Line, Tumor
  • Cystatins / immunology*
  • Cystatins / pharmacology
  • Disease Models, Animal
  • Eosinophils / drug effects
  • Eosinophils / immunology
  • Eosinophils / metabolism
  • Flow Cytometry
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism
  • Helminth Proteins / immunology*
  • Helminth Proteins / pharmacology
  • Humans
  • Immunologic Factors / pharmacology
  • Inflammation / complications
  • Inflammation / immunology*
  • Inflammation / prevention & control
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism
  • Mice
  • Respiratory Syncytial Virus Infections / complications
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Viruses / immunology*
  • Respiratory Syncytial Viruses / physiology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism


  • Cystatins
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Helminth Proteins
  • Immunologic Factors
  • Interleukin-10