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An intranasal administration of Lactococcus lactis strains expressing recombinant interleukin-10 molulates acute allergic airway inflammation in a murine model

Abstract : Background: Around 300 million people world-wide suffer from asthma, and the prevalence of allergic diseases has increased. Much effort has been used in the study of mechanisms involved in the immune response observed in asthma to intervene for the treatment of this condition. During inflammation in asthma, Th2 cytokines and eosinophils are essential components of the host immune system. Furthermore, for therapeutic interventions against this disease, IL-10 is an important cytokine because it has a central role in the regulation of inflammatory cascades. Objective: To evaluate the immunomodulatory effect of Lactococcus lactis strains expressing recombinant IL-10 in a mouse model of ovalbumin (OVA)-induced acute airway inflammation. Methods: L. lactis expressing recombinant IL-10 in a cytoplasmic (LL-CYT) or secreted form (LL-SEC) and wild-type (LL-WT) were used. IL-10 production by the recombinant strains was evaluated by ELISA. After an intranasal administration of L. lactis producing recombinant IL-10 and the induction of acute allergic airway inflammation in mice, blood samples were collected to detect IgE anti-OVA, and bronchoalveolar lavage (BAL) was harvested for eosinophil count. Additionally, the lungs were collected for the detection of the eosinophil peroxidase (EPO) activity, measurement of cytokines and chemokines and evaluation of pathology. Results: Mice that received LL-CYT and LL-SEC strains showed a significant decrease in eosinophils numbers, EPO activity, anti-OVA IgE and IgG1 levels, IL-4 and CCL3 production and pulmonary inflammation and mucus hypersecretion, compared with the asthmatic group. Only the LL-CYT/OVA group showed reduced levels of IL-5, CCL2, CCL5 and CCL11. Conclusion: Treatment with L. lactis producing recombinant IL-10 used in this study (LL-CYT and LL-SEC) modulated experimental airway inflammation in the mouse model independently of Treg cells. Additionally, the LL-CYT strain was more efficient in the suppression of lung inflammation.
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https://hal.inrae.fr/hal-02667514
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Submitted on : Sunday, May 31, 2020 - 10:49:17 AM
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Fábio A.V. Marinho, Davide Pacifico, Anderson Miyoshi, Vasco Azevedo, Yves Le Loir, et al.. An intranasal administration of Lactococcus lactis strains expressing recombinant interleukin-10 molulates acute allergic airway inflammation in a murine model. Clinical and Experimental Allergy, Wiley, 2010, 40 (10), pp.1541-1551. ⟨10.1111/j.1365-2222.2010.03502.x⟩. ⟨hal-02667514⟩

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