Lactobacillus strains reduce small intestinal injury induced by intraepithelial lymphocytes after toll-like receptor 3 activation

HORTENSIA ZELAYA; ASUKA TADA; PATRICIA CLUA; SUSANA SALVA; SUSANA ALVAREZ; HARUKI KITAZAWA; JULIO VILLENA

Buenos Aires

Congreso; The First International Joint Meeting between the Latin American Society for Immunodeficiencies (LASID), the Argentinean Society for Immunology (SAI), and the French Society for Immunology (SFI); 2015

Latin American Society for Immunodeficiencies (LASID), the Argentinean Society for Immunology (SAI), and the French Society for Immunology (SFI).

Background: intestinal intraepithelial lymphocytes (IELs) play critical roles in disrupting epithelial homeostasis after TLR3 activation with genomic rotavirus dsRNA or the synthetic dsRNA analog poly(I:C). The capacity of immunobiotic Lactobacillus rhamnosus CRL1505 (Lr05) or Lactobacillus plantarum CRL1506 (Lp06) to beneficially modulate IELs response after TLR3 activation was investigated.Methods: Lr05 or Lp06 mice were administered to different groups of adult BALB/c mice in the drinking water. The treated groups and the untreated control group were then injected intraperitoneally with poly(I:C). Intestinal tissue damage and innate immune response were studied.Results: poly(I:C) induced inflammatory-mediated intestinal tissue damage through the increase of inflammatory cells (CD3+NK1.1+, CD3+CD8αα+, CD8αα+NKG2D+) and pro-inflammatory mediators (TNF-α, IL-1β, IFN-γ, IL-15, RAE1, IL-8). Increased expression of intestinal TLR3, MDA5 and RIG-I were also observed after poly(I:C) challenge. Treatment with Lr05 or Lp06 prior to TLR3 activation significantly reduced the levels of TNF-α, IL-15, RAE1, and increased serum and intestinal IL-10. CD3+NK1.1+, CD3+CD8αα+, and CD8αα+NKG2D+ cells were also lower in lactobacilli treated mice. The immunomodulatory capacities of lactobacilli allowed a significant reduction of intestinal tissue damage.Conclusions: this work is the first demonstration of the reduction of TLR3-mediated intestinal tissue injury by immunobiotic lactobacilli through the modulation of intraepithelial lymphocytes response. It is a step forward in the understanding of the cellular mechanisms involved in the antiviral capabilities of immunobiotic strains.