Intraluminal Administration of Poly I:C Causes an Enteropathy That Is Exacerbated by Administration of Oral Dietary Antigen

Abstract

Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen.

Efficient Selection of New Immunobiotic Strains With Antiviral Effects in Local and Distal Mucosal Sites by Using Porcine Intestinal Epitheliocytes

“…We also demonstrated here that orally administered L. plantarum MPL16 is able to differentially modulate the respiratory antiviral immune response. We reported previously that the improvement of IFN-β production by CD11c + SiglecF + alveolar macrophages and IFN-γ by CD3 + CD4 + T cells is related to the ability of immunobiotic treatments to enhance resistance to respiratory virus (39,40), in line with studies demonstrating that these immune cell populations are the main producer of IFNs during pulmonary viral infections (36,37). The increased levels of respiratory IFN-γ and IFN-β found in L. plantarum MPL16-treated mice correlated with the improved resistance of mice to RSV infection.…”

“…In addition, it was reported that purified dsRNA from rotavirus is able to induce severe intestinal damage in mice through the activation of TLR3 signaling pathway (36). Moreover, it was also demonstrated that the intraperitoneal administration of the synthetic dsRNA poly(I:C) to mice mimics the inflammatory intestinal immune response elicited by rotavirus and induce mucosal erosion, villous atrophy, intestinal wall attenuation, and diarrhea (8,36,37). Interestingly, it was shown that the intestinal damage triggered by dsRNA-TRL3 interaction is mediated by the increased expression of IL-15 and retinoic acid early inducible 1 (RAE1) in IECs, which induce the activation of CD3 + NK1.1 + CD8αα + intraepithelial FIGURE 11 | Levels of bronchoalveolar lavage (BAL) interferons (IFN-β and IFN-γ), TNF-α, and interleukin 10 (IL-10) in mice orally treated with Lactobacillus rhamnosus CRL1505, Lactobacillus plantarum CRL1506, or L. plantarum MPL16 (10 8 cells/mouse per day for five consecutive days) and then challenged by the nasal route with RSV.…”

Mechanisms of innate immune activation by gluten peptide p31-43 in mice

“…Intraluminal administration of peptides and poly I:C. p31-43 peptide (LGQQQPFPPQQPY, Biomatik), nonrelated peptide (NRP) (LD-PLIRGLLARPACALQV, Think Peptides), poly I:C (Sigma Aldrich), a combination of p31-43 peptide and poly I:C, or PBS were administered intraluminally during intestinal microsurgery as previously described (3). Briefly, mice were anaesthetized with 80 mg/kg ketamine and 10 mg/kg xylazine.…”

Intestinal Innate Antiviral Immunity and Immunobiotics: Beneficial Effects against Rotavirus Infection

“…Poly(I:C), a synthetic analog of dsRNA, when administered intraperitoneally to mice mimics the local intestinal immune response elicited by an enteric viral infection (24, 25). Both purified RVs dsRNA and poly(I:C) are able to induce severe mucosal damage in the gut via TLR3 activation including villous atrophy, mucosal erosion, and gut wall attenuation (24).…”