Immunomodulatory properties of heat-killed Rhodococcus coprophilus control the allergic reaction in a mouse model of food allergy

RIZZO, GASTÓN ; QUEREDA, MICAELA; SMALDINI, PAOLA; DOCENA, GUILLERMO

Mar del Plata

Congreso; Reunión SAIC SAI SAFIS 2018; 2018

Actinomyces are non-pathogenic bacteria with immunomodulatory properties. The intestinal mucosa is lined by epithelial cells, which are key cells in gut homeostasis. We hypothesize that Actinomyces may control epithelial cells under inflammatory conditions. Our goal is to study the inhibitory effect of dead Rhodococcus coprophilus-Rc on activated cells under different pro-inflammatorystimuli and then study the immunomodulatory effect in an experimental food allergy model.Colon cell lines (Caco-2 and Caco-luc) were cultured with flagellin (FliC) and induction of cytokines (IL-1b, IL-6, TNFa) and chemokines (CCL20, IL-8 and MCP 1) were studied by qPCR. To study the immunododulatory effect in vivo, Balb/c mice were sensitized with cow´s milk proteins (CMP) plus cholera toxin by gavage, and orally challenged with CMP to evidence hypersensitivity. Previosly, Rc was orally administered during one week to modulate the immune response. Mice were challenged and treatment efficacy was in vivo (clinical score and cutaneous test) and in vitro (serum specific antibodies and cytokines by ELISA, and cell analysis by flow cytometry) evaluated.We found that despite the response of Caco-2-luc to live and dead Salmonella typhimurium, they were unresponsive to Rc. However, when cells were previously activated, Rc inhibited the induction of cytokines and chemokines. By western blot we defined that this effect could be due a reduction of p65 translocation to the nucleus. This inhibitory effect was also observed in mouse orally exposed to cholera toxin. Intragastric administration of Rc down modulated the expression of CCL20 in gut.In the CMP allergy mouse model, clinical signs and serum specific IgE levels were lower in Rc- treated mice compared with sensitized mice (p