title: The Helminth-Derived Immunomodulator AvCystatin Reduces Virus Enhanced Inflammation by Induction of Regulatory IL-10+ T Cells.
abstract: 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.
authors: Respiratory Science Division, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors: Martijn J
authors: MJ
authors: Schuijs
authors: Centre for Infection Medicine, Institute for Immunology, Freie Universität Berlin, Berlin, Germany.
authors: Susanne
authors: S
authors: Hartmann
authors: Department of Life Sciences, Imperial College London, London, United Kingdom.
authors: Murray E
authors: ME
authors: Selkirk
authors: Department of Life Sciences, Imperial College London, London, United Kingdom.
authors: Luke B
authors: LB
authors: Roberts
authors: Respiratory Science Division, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors: Peter J M
authors: PJ
authors: Openshaw
authors: Respiratory Science Division, National Heart and Lung Institute, Imperial College London, London, United Kingdom.|Department of Life Sciences, Imperial College London, London, United Kingdom.
authors: Corinna
authors: C
authors: Schnoeller
mesh_terms: D000818:Animals; D001988:Bronchiolitis / Q000150:complications / Q000276:immunology / Q000517:prevention & control; D045744:Cell Line, Tumor; D015891:Cystatins / Q000276:immunology* / Q000494:pharmacology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D015801:Helminth Proteins / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D007249:Inflammation / Q000150:complications / Q000276:immunology* / Q000517:prevention & control; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D015891:Cystatins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015801:Helminth Proteins; D007155:Immunologic Factors; D016753:Interleukin-10