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

Date

2020-11-01

Author

Bulut, Esin Alpdundar
Kocabas, Banu Bayyurt
Yazar, Volkan
Aykut, Gamze
GÜLER, ÜLKÜ
SALİH, BEKİR
Yilmaz, Naz Surucu
Ayanoğlu, İhsan Cihan
Polat, Muammer Merve
AKÇALI, KAMİL CAN
GÜRSEL, İHSAN
Gürsel, Mayda

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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.

URI

https://hdl.handle.net/11511/69616

Journal

JOURNAL OF IMMUNOLOGY

DOI

https://doi.org/10.4049/jimmunol.2000731

Collections

Department of Biology, Article

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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: https://hdl.handle.net/11511/69616.