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Lactobacillus reuteri–induced Regulatory T cells Protect against an Allergic Airway Response in Mice

¹ The Brain-Body Institute and ² Firestone Institute for Respiratory Health, Departments of ³ Medicine and ⁴ Pathology and Molecular Medicine, McMaster University and St Joseph's Healthcare, Hamilton, Ontario, Canada

Correspondence and requests for reprints should be addressed to Paul Forsythe, Ph.D., The Brain-Body Institute, St. Joseph's Healthcare, 50 Charlton Avenue East, T3312, Hamilton, ON L8N 4A6, Canada. E-mail: forsytp{at}mcmaster.ca

Rationale: We have previously demonstrated that oral treatment with live Lactobacillus reuteri can attenuate major characteristics of the asthmatic response in a mouse model of allergic airway inflammation. However, the mechanisms underlying these effects remain to be determined.

Objectives: We tested the hypothesis that regulatory T cells play a major role in mediating L. reuteri–induced attenuation of the allergic airway response.

Methods: BALB/c mice were treated daily with L. reuteri by gavage. Flourescent-activated cell sorter analysis was used to determine CD4⁺CD25⁺Foxp3⁺T cell populations in spleens following treatment with L. reuteri or vehicle control. Cell proliferation assays were performed on immunomagnetic bead separated CD4⁺CD25⁺ and CD4⁺CD25^– T cells. CD4⁺CD25⁺ T cells isolated from, ovalbumin naive, L. reuteri treated mice were transferred into ovalbumin-sensitized mice. Following antigen challenge the airway responsiveness, inflammatory cell influx and cytokine levels in bronchoalveolar lavage fluid of recipient mice were assessed.

Measurements and Main Results: Following 9 days of oral L. reuteri treatment, the percentage and total number of CD4⁺CD25⁺Foxp3⁺T cells in spleens significantly increased. CD4⁺CD25⁺ cells isolated from L. reuteri–fed animals also had greater capacity to suppress T-effector cell proliferation. Adoptive transfer of CD4⁺CD25⁺ T cells from L. reuteri–treated mice to ovalbumin-sensitized animals attenuated airway hyper-responsiveness and inflammation in response to subsequent antigen challenge.

Conclusions: These results strongly support a role for nonantigen-specific CD4⁺CD25⁺Foxp3⁺ regulatory T cells in attenuating the allergic airway response following oral treatment with L. reuteri. This potent immuno-regulatory action may have therapeutic potential in controlling the Th2 bias observed in atopic individuals.

Key Words: commensal bacteria • Foxp3 • airway inflammation • allergy

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Although there is evidence that exposure to certain commensal bacteria can reduce allergic responses the exact mechanisms behind these effects are still obscure. What This Study Adds to the Field This study provides evidence that oral treatment with a Lactobacillus strain induces regulatory T cells that can attenuate the allergic airway response in a nonantigen-specific manner.

 

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