REGULATORY T CELLS INDUCED BY ACTINOMYCES BACTERIA CONTROLLED THE ALLERGIC REACTION IN A MOUSE MODEL OF FOOD ALLERGY

SMALDINI PAOLA LORENA; TREJO, FERNANDO M; MAHAVIR SINGH; KAMPINGA, JAAP; DOCENA, GUILLERMO H

Congreso; I meeting LASID-FAIC-SAI; 2015

Food allergy isan immune-mediated adverse reaction to food likely due to defective regulatorycircuits. In this work we aimed to modulate milk allergy in a mouse modelthrough the oral administration of a heat-killed Actinomyces bacteria(Tsukamurella inchonensis-Ti) and to study the immunomodulatory mechanisms. Balb/c mice were sensitized with cow´s milk proteins(CMP) plus cholera toxin by gavage, and orally challenged with CMP to evidencehypersensitivity symptoms. Thereafter, heat-killed Ti was orally administeredas treatment. Mice were challenged and treatment efficacy was in vivo (clinical score and cutaneoustest) and in vitro (serum specificantibodies and cytokines-ELISA, and cell analysis-flow cytometry) evaluated.Clinical signswere lower in Ti-treated mice compared with milk-sensitized mice (average score-1for Ti-Treated vs average score-3 for milk-sensitized mice; p<0.05), serum CMPspecific IgE and IgG1 levels were lower in Ti-treated mice with a concomitantreduction of IL-4 and IL-5 (p<0,01). Ti-treated mice showed an increasedfrequency of lamina propria CD4+CD25+FoxP3+T cells (9.61±2.15% vs 6.15±0.25%Ti-treated and Sensitized, respectively) (p<0,01). Intestinal IL-10 andIL-10+FoxP3+T cells were up-regulated in Ti-treated mice. In vivo depletion of Tregs(anti-CD25) abrogated Ti immunomodulation, and mice showed higher clinicalscore and serum IgE compared with non-depleted mice. Finally, we showedthat heat-killed Ti and the Ti-derived proprietary recombinant proteins(ACT-108 and ACT-109) induced thesecretion of IL-10 by macrophages.In conclusion,Ti orally induced Treg that controlled the Th2-mediated allergic responses,with suppression of IgE. These findings may constitute the basis for apotential immunotherapy for food allergies.