Immunobiotic Lactobacillus strains reduce small intestinal injury induced by intraepithelial lymphocytes after Toll-like receptor 3 activation.
OBJECTIVE
Intestinal intraepithelial lymphocytes (IELs) play critical roles in disrupting epithelial homeostasis after Toll-like receptor (TLR)-3 activation with genomic rotavirus dsRNA or the synthetic dsRNA analog poly(I:C). The capacity of immunobiotic Lactobacillus rhamnosus CRL1505 (Lr1505) or Lactobacillus plantarum CRL1506 (Lp1506) to beneficially modulate IELs response after TLR3 activation was investigated in vivo using a mice model.


RESULTS
Intraperitoneal administration of 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 was also observed after poly(I:C) challenge. Treatment with Lr1505 or Lp1506 prior to TLR3 activation significantly reduced the levels of TNF-α, IL-15, RAE1, and increased serum and intestinal IL-10. Moreover, CD3(+)NK1.1(+), CD3(+)CD8αα(+), and CD8αα(+)NKG2D(+) cells were lower in lactobacilli-treated mice when compared to controls. The immunomodulatory capacities of lactobacilli allowed a significant reduction of intestinal tissue damage.


CONCLUSIONS
This work demonstrates 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.
Immunobiotics Research Group, Tucuman, Argentina.|Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina.|Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.|Livestock Immunology Unit, International Education and Research Center for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
Asuka
A
Tada
Immunobiotics Research Group, Tucuman, Argentina.|Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina.
Hortensia
H
Zelaya
Immunobiotics Research Group, Tucuman, Argentina.|Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina.
Patricia
P
Clua
Immunobiotics Research Group, Tucuman, Argentina.|Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina.
Susana
S
Salva
Immunobiotics Research Group, Tucuman, Argentina.|Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina.
Susana
S
Alvarez
Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan. haruki.kitazawa.c7@tohoku.ac.jp.|Livestock Immunology Unit, International Education and Research Center for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan. haruki.kitazawa.c7@tohoku.ac.jp.
Haruki
H
Kitazawa
Immunobiotics Research Group, Tucuman, Argentina. jcvillena@cerela.org.ar.|Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina. jcvillena@cerela.org.ar.|Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan. jcvillena@cerela.org.ar.
Julio
J
Villena
D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D001219:Aspartate Aminotransferases / Q000097:blood; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004751:Enteritis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D007419:Intestinal Secretions / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D048191:Lactiplantibacillus plantarum; D052201:Lacticaseibacillus rhamnosus; D007958:Leukocyte Count; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008807:Mice, Inbred BALB C; D011070:Poly I-C; D019936:Probiotics / Q000627:therapeutic use*; D051196:Toll-Like Receptor 3 / Q000819:agonists*
D016207:Cytokines; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D011070:Poly I-C
Immunobiotics; Intestinal damage; Intraepithelial lymphocytes; Lactobacilli; Poly(I:C); TLR3