title: Pretreatment with a heat-killed probiotic modulates monocyte chemoattractant protein-1 and reduces the pathogenicity of influenza and enterovirus 71 infections.
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.
authors.affiliation: Research Center for Emerging Viral Infections, Chang Gung University, Tao-Yuan, Taiwan, ROC.
authors.forename: M-F
authors.initials: MF
authors.lastname: Chen
authors.affiliation: Research Center for Emerging Viral Infections, Chang Gung University, Tao-Yuan, Taiwan, ROC.
authors.forename: K-F
authors.initials: KF
authors.lastname: Weng
authors.affiliation: Research Center for Emerging Viral Infections, Chang Gung University, Tao-Yuan, Taiwan, ROC.|Graduate Institute of Biomedical Sciences, Chang Gung University, Tao-Yuan, Taiwan, ROC.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Research Center for Emerging Viral Infections, Chang Gung University, Tao-Yuan, Taiwan, ROC.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Research Center for Emerging Viral Infections, Chang Gung University, Tao-Yuan, Taiwan, ROC.
authors.forename: S-N
authors.initials: SN
authors.lastname: Tseng
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Tao-Yuan, Taiwan, ROC.|Department of Biomedical Sciences, University of the Pacific, Arthur Dugoni School of Dentistry, San Francisco, California, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Ojcius
authors.affiliation: Research Center for Emerging Viral Infections, Chang Gung University, Tao-Yuan, Taiwan, ROC.|Graduate Institute of Biomedical Sciences, Chang Gung University, Tao-Yuan, Taiwan, ROC.|Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Tao-Yuan, Taiwan, ROC.|Clinical Virology Laboratory, Department of Clinical Pathology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, ROC.
authors.forename: S-R
authors.initials: SR
authors.lastname: Shih
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D013293:Enterococcus faecalis / Q000276:immunology*; D029821:Enterovirus A, Human / Q000276:immunology* / Q000472:pathogenicity; D004769:Enterovirus Infections / Q000276:immunology*; D006358:Hot Temperature; D006801:Humans; D056747:Immunomodulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009975:Orthomyxoviridae / Q000276:immunology* / Q000472:pathogenicity; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D019936:Probiotics / Q000008:administration & dosage*; D054390:Receptors, CCR2 / Q000235:genetics
chemical_list: C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054390:Receptors, CCR2