ABSTRACT
It has been proposed that inactivated probiotics may modulate the host immune system and contribute to mitigation of viral infections. This study demonstrated that administration of heat-killed Enterococcus faecalis, a widely used probiotic, can protect host animals against viral infections. The influenza-mediated morbidity and lung inflammation in E. faecalis-treated mice decreased significantly compared with those of the control mice. Furthermore, we found that the protection is associated with production of monocyte chemoattractant protein-1 (MCP-1). The intratracheal injection of a recombinant mouse MCP-1 protein abrogated the antiviral effects elicited by pretreatment with E. faecalis. CC chemokine receptor 2 (CCR2) is a receptor for MCP-1, and the intraperitoneal administration of a CCR2 antagonist effectively inhibited viral pathogenicity. The reduced pathogenicity was also observed in CCR2-deficient mice. Finally, E. faecalis significantly attenuated neuropathogenicity induced by another RNA virus, enterovirus 71. This study demonstrates that killed probiotics can reduce viral disease severity and identify that the MCP-1 pathway might act as a key mediator in the improved antiviral immune response. Our findings suggest that MCP-1 and its related signaling pathway can serve as critical therapeutic targets for development of new antiviral strategies.
Subject(s)
Chemokine CCL2/metabolism , Enterococcus faecalis/immunology , Enterovirus A, Human/immunology , Enterovirus Infections/immunology , Orthomyxoviridae Infections/immunology , Orthomyxoviridae/immunology , Probiotics/administration & dosage , Animals , Cells, Cultured , Enterovirus A, Human/pathogenicity , Hot Temperature , Humans , Immunomodulation , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Orthomyxoviridae/pathogenicity , Receptors, CCR2/geneticsABSTRACT
Two humic-like substances, the oxidative polymer of protocatechuic acid (OP-PCA) and humic acid inhibit the in vitro replication of influenza virus A/WSN/33 (H1N1) in Madin-Darby canine kidney (MDCK) cells at concentrations of no cytotoxicity. The 50% inhibitory concentration (IC50) for OP-PCA was 6.59 +/- 1.02 microg/ml when the compound was added at the stage of viral adsorption. When OP-PCA was added after virus adsorption, the IC50 was 53.27 +/- 8.12 microg/ml. The IC50 for humic acid was 48.61 +/- 7.32 microg/ml and 55.27 +/- 5.46 microg/ml respectively when the compound was added at the stage of viral adsorption or post-adsorption. In spite of structural resemblance of these two compounds, they exhibit different actions of anti-flu. The OP-PCA inhibits virus-induced hemagglutination and low pH-induced cell-cell fusion. Humic acid inhibits the endonuclease activity of viral RNA polymerase. The monomer of PCA shows no inhibition on influenza virus replication.
