Protective effect of Schistosoma mansoni infection on allergic airway inflammation depends on the intensity and chronicity of infection
Background: Population studies have suggested that chronic and intense helminth infections, in contrast to acute and mild helminth infections, might suppress allergic airway inflammation. Objective: We sought to address the question of how the chronicity and intensity of helminth infections affect allergic airway inflammation in a well-defined experimental model. Methods: C57/Bl6 mice were infected with Schistosoma mansoni, followed by sensitization and challenge with ovalbumin (OVA), and different stages and intensities of infection were studied. To this end, mice were analyzed at 8, 12, or 16 weeks, representing the acute, intermediate, or chronic phases of infection, respectively. Results: Lung lavage eosinophilia, peribronchial inflammation, and OVA-induced airway hyperresponsiveness were increased during acute infection but significantly decreased when infection progressed into chronicity. Decreases in lung lavage eosinophilia were parasite density-dependent. Similar levels of OVA-specific IgE were found during all phases of infection, whereas both OVA-specific and parasite-specific TH2 cytokine levels were significantly reduced during chronic infection. Inhibition of airway inflammation could be transferred to OVA-sensitized recipient mice by B cells and CD4+T cells from spleens of chronically, but not acutely, infected mice. This suppression was IL-10-dependent. Conclusion: During chronic, but not acute, helminth infections, suppressive mechanisms are induced that regulate immune reactions to inhaled allergens. These data confirm human epidemiologic observations in a well-controlled animal model. Clinical implications: Characterization of chronic helminth infection-induced regulatory mechanisms will help in the development of future therapeutics to treat or prevent allergic disease.
|Keywords||IL-10, allergy, helminth, immune suppression, regulatory B cells, regulatory T cells|
|Persistent URL||dx.doi.org/10.1016/j.jaci.2007.06.009, hdl.handle.net/1765/35160|
Smits, H.H., Hammad, H., van Nimwegen, M., Soullié, T., Willart, M.A., Lievers, E., … Yazdanbakhsh, M.. (2007). Protective effect of Schistosoma mansoni infection on allergic airway inflammation depends on the intensity and chronicity of infection. Journal of Allergy and Clinical Immunology, 120(4), 932–940. doi:10.1016/j.jaci.2007.06.009