Adhesion to the intestinal mucosa is not necessary for Lactobacillus rhamnosus CRL1505 to exert its immunomodulatory activities in local and distal mucosal sites

Abstract

Both, viable and non-viable orally administered Lactobacillus rhamnosus CRL1505 modulate immunity in local (intestine) and distal (respiratory) mucosal sites. Then, intestinal adhesion and colonization would not be necessary for the immunomodulatory effects of this immunobiotic strain. In this work, a mucus-binding factor knockout CRL1505 strain (ΔmbfCRL1505) was obtained and the lack of binding ability to both intestinal epithelial cells and mucin was demonstrated in vitro. Two sets of in vivo experiments in 6-week-old Balb/c mice were performed to evaluate ΔmbfCRL1505 immunomodulatory activities. A) Orally administered ΔmbfCRL1505 prior intraperitoneal injection of the TLR3 agonist poly(I:C) significantly reduced (p<0.01) intraepithelial lymphocytes (CD3+NK1.1+CD8αα+) and pro-inflammatory mediators (TNF-α, IL-6 and IL-15) in the intestinal mucosa. B) Orally administered ΔmbfCRL1505 prior nasal stimulation with poly(I:C) significantly decreased (p<0.05) the levels of the biochemical markers of lung tissue damage. In addition, reduced recruitment of neutrophils and levels of pro-inflammatory mediators (TNF-α, IL-6 and IL-8) in the respiratory mucosa were observed in ΔmbfCRL1505-treated mice when compared to untreated control mice (p<0.05). The immunological changes induced by ΔmbfCRL1505 strain were not different from those previously reported for the wild-type CRL1505 strain. Although it is generally accepted that the adhesion to the intestinal mucosa is necessary for immunobiotics to induce their beneficial effects, it was demonstrated here, that this property is not required for L. rhamnosus CRL1505 to exert its immunomodulatory activities in local and distal mucosal sites. These results are a step forward in the understanding of the mechanisms involved in the immunomodulatory capabilities of L. rhamnosus CRL1505.