PMID- 27072606 OWN - NLM STAT- MEDLINE DCOM- 20171013 LR - 20230203 IS - 1935-3456 (Electronic) IS - 1933-0219 (Linking) VI - 10 IP - 1 DP - 2017 Jan TI - Pretreatment with a heat-killed probiotic modulates monocyte chemoattractant protein-1 and reduces the pathogenicity of influenza and enterovirus 71 infections. PG - 215-227 LID - 10.1038/mi.2016.31 [doi] AB - 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. FAU - Chen, M-F AU - Chen MF AD - Research Center for Emerging Viral Infections, Chang Gung University, Tao-Yuan, Taiwan, ROC. FAU - Weng, K-F AU - Weng KF AD - Research Center for Emerging Viral Infections, Chang Gung University, Tao-Yuan, Taiwan, ROC. FAU - Huang, S-Y AU - Huang SY AD - Research Center for Emerging Viral Infections, Chang Gung University, Tao-Yuan, Taiwan, ROC. AD - Graduate Institute of Biomedical Sciences, Chang Gung University, Tao-Yuan, Taiwan, ROC. FAU - Liu, Y-C AU - Liu YC AD - Research Center for Emerging Viral Infections, Chang Gung University, Tao-Yuan, Taiwan, ROC. FAU - Tseng, S-N AU - Tseng SN AD - Research Center for Emerging Viral Infections, Chang Gung University, Tao-Yuan, Taiwan, ROC. FAU - Ojcius, D M AU - Ojcius DM AD - Center for Molecular and Clinical Immunology, Chang Gung University, Tao-Yuan, Taiwan, ROC. AD - Department of Biomedical Sciences, University of the Pacific, Arthur Dugoni School of Dentistry, San Francisco, California, USA. FAU - Shih, S-R AU - Shih SR AD - Research Center for Emerging Viral Infections, Chang Gung University, Tao-Yuan, Taiwan, ROC. AD - Graduate Institute of Biomedical Sciences, Chang Gung University, Tao-Yuan, Taiwan, ROC. AD - Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Tao-Yuan, Taiwan, ROC. AD - Clinical Virology Laboratory, Department of Clinical Pathology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, ROC. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160413 PL - United States TA - Mucosal Immunol JT - Mucosal immunology JID - 101299742 RN - 0 (Ccl2 protein, mouse) RN - 0 (Ccr2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Receptors, CCR2) SB - IM MH - Animals MH - Cells, Cultured MH - Chemokine CCL2/*metabolism MH - Enterococcus faecalis/*immunology MH - Enterovirus A, Human/*immunology/pathogenicity MH - Enterovirus Infections/*immunology MH - Hot Temperature MH - Humans MH - Immunomodulation MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Orthomyxoviridae/*immunology/pathogenicity MH - Orthomyxoviridae Infections/*immunology MH - Probiotics/*administration & dosage MH - Receptors, CCR2/genetics EDAT- 2016/04/14 06:00 MHDA- 2017/10/14 06:00 CRDT- 2016/04/14 06:00 PHST- 2015/10/15 00:00 [received] PHST- 2016/02/29 00:00 [accepted] PHST- 2016/04/14 06:00 [pubmed] PHST- 2017/10/14 06:00 [medline] PHST- 2016/04/14 06:00 [entrez] AID - S1933-0219(22)00636-5 [pii] AID - 10.1038/mi.2016.31 [doi] PST - ppublish SO - Mucosal Immunol. 2017 Jan;10(1):215-227. doi: 10.1038/mi.2016.31. Epub 2016 Apr 13.