PMID- 28288575 OWN - NLM STAT- MEDLINE DCOM- 20171129 LR - 20220408 IS - 1471-2180 (Electronic) IS - 1471-2180 (Linking) VI - 17 IP - 1 DP - 2017 Mar 14 TI - Lactobacillus-derived extracellular vesicles enhance host immune responses against vancomycin-resistant enterococci. PG - 66 LID - 10.1186/s12866-017-0977-7 [doi] LID - 66 AB - BACKGROUND: Probiotic bacteria are known to modulate host immune responses against various pathogens. Recently, extracellular vesicles (EVs) have emerged as potentially important mediators of host-pathogen interactions. In this study, we explored the role of L. plantarum derived EVs in modulating host responses to vancomycin-resistant Enterococcus faecium (VRE) using both Caenorhabditis elegans and human cells. RESULTS: Our previous work has shown that probiotic conditioning C. elegans with L. acidophilus NCFM prolongs the survival of nematodes exposed to VRE. Similarly, L. plantarum WCFS1 derived extracellular vesicles (LDEVs) also significantly protected the worms against VRE infection. To dissect the molecular mechanisms of this EV-induced protection, we found that treatment of C. elegans with LDEVs significantly increased the transcription of host defense genes, cpr-1 and clec-60. Both cpr-1 and clec-60 have been previously reported to have protective roles against bacterial infections. Incubating human colon-derived Caco-2 cells with fluorescent dye-labeled LDEVs confirmed that LDEVs could be transported into the mammalian cells. Furthermore, LDEV uptake was associated with significant upregulation of CTSB, a human homologous gene of cpr-1, and REG3G, a human gene that has similar functions to clec-60. CONCLUSIONS: We have found that EVs produced from L. plantarum WCFS1 up-regulate the expression of host defense genes and provide protective effects on hosts. Using probiotic-derived EVs instead of probiotic bacteria themselves, this study provides a new direction to treat antimicrobial resistant pathogens, such as VRE. FAU - Li, Ming AU - Li M AD - Division of Infectious Diseases, The Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA. ming.li@brown.edu. FAU - Lee, Kiho AU - Lee K AD - Division of Infectious Diseases, The Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA. FAU - Hsu, Min AU - Hsu M AD - Division of Infectious Diseases, The Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA. FAU - Nau, Gerard AU - Nau G AD - Division of Infectious Diseases, The Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA. FAU - Mylonakis, Eleftherios AU - Mylonakis E AD - Division of Infectious Diseases, The Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA. FAU - Ramratnam, Bharat AU - Ramratnam B AD - Division of Infectious Diseases, The Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA. AD - COBRE Center for Cancer Research, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA. AD - Clinical Research Center of Lifespan, Providence, RI, 02903, USA. LA - eng GR - K24 HD080539/HD/NICHD NIH HHS/United States GR - P30 GM110759/GM/NIGMS NIH HHS/United States GR - R01 HD072693/HD/NICHD NIH HHS/United States GR - U54 GM115677/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20170314 PL - England TA - BMC Microbiol JT - BMC microbiology JID - 100966981 SB - IM MH - Animals MH - Caco-2 Cells/immunology/microbiology MH - Caenorhabditis elegans/genetics/immunology/microbiology MH - Cell Survival MH - Extracellular Vesicles/*immunology/*metabolism/ultrastructure MH - Gene Expression Regulation MH - Gram-Positive Bacterial Infections/microbiology MH - Host-Pathogen Interactions/*immunology MH - Humans MH - Lactobacillus/*metabolism MH - Lactobacillus plantarum/metabolism MH - Microscopy, Electron MH - Probiotics/*therapeutic use MH - Vancomycin-Resistant Enterococci/*immunology/*pathogenicity PMC - PMC5348868 OTO - NOTNLM OT - CTSB OT - Extracellular vesicles OT - LDEVs OT - Lactobacillus OT - REG3G OT - VRE OT - Vancomycin-resistant enterococci EDAT- 2017/03/16 06:00 MHDA- 2017/12/01 06:00 PMCR- 2017/03/14 CRDT- 2017/03/15 06:00 PHST- 2016/11/04 00:00 [received] PHST- 2017/03/09 00:00 [accepted] PHST- 2017/03/15 06:00 [entrez] PHST- 2017/03/16 06:00 [pubmed] PHST- 2017/12/01 06:00 [medline] PHST- 2017/03/14 00:00 [pmc-release] AID - 10.1186/s12866-017-0977-7 [pii] AID - 977 [pii] AID - 10.1186/s12866-017-0977-7 [doi] PST - epublish SO - BMC Microbiol. 2017 Mar 14;17(1):66. doi: 10.1186/s12866-017-0977-7.