Human Gut Commensal Membrane Vesicles Modulate Inflammation by Generating M2-like Macrophages and Myeloid-Derived Suppressor Cells

Bulut, Esin Alpdundar
Kocabas, Banu Bayyurt
Yazar, Volkan
Aykut, Gamze
Yilmaz, Naz Surucu
Ayanoğlu, İhsan Cihan
Polat, Muammer Merve
Gürsel, Mayda
Immunomodulatory commensal bacteria modify host immunity through delivery of regulatory microbial-derived products to host cells. Extracellular membrane vesicles (MVs) secreted from symbiont commensals represent one such transport mechanism. How MVs exert their anti-inflammatory effects or whether their tolerance-inducing potential can be used for therapeutic purposes remains poorly defined. In this study, we show that MVs isolated from the human lactic acid commensal bacteria Pediococcus pentosaceus suppressed Ag-specific humoral and cellular responses. MV treatment of bone marrow-derived macrophages and bone marrow progenitors promoted M2-like macrophage polarization and myeloid-derived suppressor cell differentiation, respectively, most likely in a TLR2-dependent manner. Consistent with their immunomodulatory activity, MV-differentiated cells upregulated expression of IL-10, arginase-1, and PD-L1 and suppressed the proliferation of activated T cells. MVs' antiinflammatory effects were further tested in acute inflammation models in mice. In carbon tetrachloride-induced fibrosis and zymosan-induced peritonitis models, MVs ameliorated inflammation. In the dextran sodium sulfate-induced acute colitis model, systemic treatment with MVs prevented colon shortening and loss of crypt architecture. In an excisional wound healing model, i.p. MV administration accelerated wound closure through recruitment of PD-L1-expressing myeloid cells to the wound site. Collectively, these results indicate that P pentosaceus-derived MVs hold promise as therapeutic agents in management/treatment of inflammatory conditions.


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Küçükünsal, Serkan; İçgen, Bülent; Department of Environmental Engineering (2019)
Wastewater treatment plants (WWTPs) as hotspots of the antibiotic resistance genes (ARGs) pose risk to receiving environments. Removal of ARGs through WWTPs, therefore, is great importance. For this reason, common types of WWTPs including conventional activated sludge (CAS), biological nutrient removal (BNR), sequencing batch reactor (SBR), membrane bioreactor (MBR), package MBR, WWTP with coagulation-flocculation and UV disinfection units were investigated in terms of their seasonal removal efficiencies on...
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Klinman, DM; Zeuner, R; Yamada, H; Gürsel, Mayda; Currie, D; Gursel, I (Wiley, 2003-12-01)
Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated "CpG motifs" stimulate an innate immune response characterized by the production of cytokines, chemokines, and polyreactive Igs that promote host survival following infectious challenge. Yet CpG-driven immune activation can have deleterious consequences, such as increasing the host's susceptibility to autoimmune disease. The immunomodulatory activity of CpG DNA can be blocked by DNA containing "suppressive" motifs. This work exp...
Live-cell imaging of Pol II promoter activity to monitor gene expression with RNA IMAGEtag reporters
SHIN, Ilchung; RAY, Judhajeet; Gupta, Vinayak; İlgü, Müslüm; Beasley, Jonathan; BENDICKSON, Lee; MEHANOVIC, Samir; Kraus, George A.; Nilsen-Hamilton, Marit (Oxford University Press (OUP), 2014-01-01)
We describe a ribonucleic acid (RNA) reporter system for live-cell imaging of gene expression to detect changes in polymerase II activity on individual promoters in individual cells. The reporters use strings of RNA aptamers that constitute IMAGEtags (Intracellular MultiAptamer GEnetic tags) that can be expressed from a promoter of choice. For imaging, the cells are incubated with their ligands that are separately conjugated with one of the FRET pair, Cy3 and Cy5. The IMAGEtags were expressed in yeast from ...
Human peripheral blood cells differentially recognize and respond to two distinct CpG motifs
Verthelyi, D; Ishii, KJ; Gürsel, Mayda; Takeshita, F; Klinman, DM (The American Association of Immunologists, 2001-02-15)
Oligodeoxynucleotides (ODN) that contain unmethylated CpG dinucleotides trigger a strong innate immune response in vertebrates. CpG ODN show promise as vaccine adjuvants, anti-allergens, and immunoprotective agents in animal models. Their transition to clinical use requires the identification of motifs that are optimally stimulatory in humans. Analysis of hundreds of novel ODN resulted in the identification and characterization of two structurally distinct "clusters" of immunostimulatory CpG ODN, One cluste...
Differential activation of immune cells by commensal versus pathogen-derived bacterial DNA
Günalp, Sinem; Gürsel, Mayda; Department of Biology (2015)
Immunological mechanisms making contribution to discriminating signals obtained from commensal versus pathogenic bacteria is an active area of research and recent evidence proposes that commensals and pathogens might express discrete variants of pathogen associated molecular patterns (PAMP). We hypothesized that as a major member of PAMP, bacterial DNA (bacDNA) originating from commensals versus pathogens might possess distinct immunostimulatory activities, enabling their dis- crimination by the immune syst...
Citation Formats
E. A. Bulut et al., “Human Gut Commensal Membrane Vesicles Modulate Inflammation by Generating M2-like Macrophages and Myeloid-Derived Suppressor Cells,” JOURNAL OF IMMUNOLOGY, pp. 2707–2718, 2020, Accessed: 00, 2020. [Online]. Available: