TABLE 2.
Immunomodulatory effect of exosomes derived from immune cells in sepsis.
| Donor cell | Contents | Transfer pathway | Target cell | Signaling pathway/Protein | Immuno-effect | Immune outcome | References |
|---|---|---|---|---|---|---|---|
| Macrophage | 19KD lipoprotein | N/A | Macrophage | TLR2-MyD88 (+), CIITA (−) | MHC-II ↓, CD64 ↓ | Suppression | Ojcius et al. (2011) |
| Macrophage | HSP70 | N/A | Macrophage | NF-κB (+) | Macrophage mutation and phagocytosis ↑, TNF-α ↑ | Activation | Neyrolles et al. (2010) |
| Macrophage, THP1 | PAMPs (19KD lipoprotein, LAM, LPS) | N/A | Macrophage | TLR2/4-MyD88 (+) | Macrophage and neutrophil recruitment ↑, macrophage activation ↑, TNF-1/α ↑, IL-12 ↑ | Activation | Bhatnagar et al. (2007) |
| Macrophage | miR-146a | N/A | Neutrophil | SOD (−) | ROS ↑, NETs ↑ | Activation | Zhang et al. (2019b) |
| Alveolar macrophage | MV a : TNF | N/A | Alveolar epithelial cell | N/A | ICAM-1 ↑ | Activation | Soni et al. (2016) |
| Macrophage | N/A | N/A | Macrophage | NF-κB (+) | TNF-α ↑ | Activation | Li et al. (2018b) |
| Macrophage | N/A | N/A | PMN | NADPH oxidase (+) | ROS ↑, pyroptosis ↑ | Activation | Jiao et al. (2017) |
| Macrophage | N/A | N/A | HUVEC | Integrin β1 ubiquitin, internalization and degradation (+), integrin β1 recycle to endosome (−), MEK-ERK (−) | MMP9 ↓, ECs migration ↓ | N/A | Lee et al. (2014) |
| Macrophage | N/A | N/A | Hepatocyte | NOD (+) | NLRP3 ↑ | Activation | Wang et al. (2018a) |
| Macrophage | MV a : Histone | N/A | Naive macrophage | TLR4 (+) | TNF-α ↑, IL-6 ↑, IL-1β ↑ | Activation | Nair et al. (2018) |
| Macrophage | miR-126-5p, miR-146a/b, miR-21-3p, let7b, mRNA (encoding GADPH, CXCL2, CCL2/4, TNF-α), Ieb2, creb, G-CSF, IL-1Ra, TNF-α, chemokines | N/A | Macrophage | TLR-NF-κB | Anti-inflammation, pro-inflammation | Suppression/Activation | McDonald et al. (2014) |
| MDM, MDDC, PMNL | LTC4S, LTA4H, 5-LO | TGF-β1 | PMNL | 5-KETE (+), LTA4-LTB4-LTC4 (+) | PMNL chemotaxis ↑, inflammatory cytokines ↑ | Activation | Esser et al. (2010) |
| Macrophage | IL-1β, NLRP3 | ATP/P2X7R | N/A | NF-κB (+) | Inflammatory cytokines ↑ | Activation | Qu et al. (2007) |
| Monocyte | MP a : mt DNA | N/A | PMNs | TLR9 (+) | PMNs chemotaxis ↓ | Suppression | Konecna et al. (2021) |
| Monocyte | N/A | N/A | Monocyte | TLR4 (−) | TNF-α ↓ | Suppression | Wisler et al. (2020) |
| Monocyte | miR-155, miR-223 | N/A | ECs (direct) PMNs (indirect) | TLR4-NF-κB (+) | ICAM-1 ↑, CCL-2 ↑, IL-6 ↑, monocyte chemotaxis and adhesion ↑ | Activation | Tang et al. (2016) |
| Monocyte (THP1) | ATP | SLC179A | THP1 | P2Y11 (+) | M1 phenotype ↑, IL-6 ↑ | Activation | Sakaki et al. (2013) |
| PMN | MP a : AnxA1 | N/A | PMNs | ALX (bind to AnxA1) | PMNs chemotaxis and adhesion ↓ | Suppression | Dalli et al. (2008) |
| PMN | MP a : Anti-inflammatory cytokines (late stage in sepsis), PS | N/A | THP1 Macrophage | N/A | THP1 (MP): TGF-α ↑, PGE2 ↑, IL-10 ↑, THP1 (bystander): activity ↓, M2 ↑, M1 ↓ | Suppression | Prakash et al. (2012) |
| PMN | PS | N/A | IMoDC | TLR4 (+) | iMoDC maturation, phagocytosis and chemotaxis ↓, induce T cell proliferation ↓, TGF-β1 ↑, CCR7 ↓ | Suppression | Eken et al. (2008) |
| IDC (immature dendritic cell) | MFGE8 | N/A | Macrophage | N/A | Phagocytosis ↑ (direct), TNF-α ↓, HMGB1 ↓ (indirect) | Activation (direct) Suppression (indirect) | Miksa et al. (2009) |
| BMDC | EVs a : TLR4 | N/A | BMDC | NF-κB (+) | IL-6 ↑, TNF-α ↑ | Activation | Zhang et al. (2019a) |
| DC | ICAM-1, MHC-II-peptide, CD86, MFG-E8 | ICAM-1/LFA-1, ICAM-1/Mac-1 | Naive T cell B cell Macrophage | ICAM-1/LFA-1 (+), ICAM-1/Mac-1 (+), MHC-II-peptide/TCR (+) | Naive T cell activation ↑, T Cell proliferation ↑, Transfer the ability of priming naive T cells to B cell and macrophage | Activation | Segura et al. (2005) |
| IDC | MFGE8 | N/A | Macrophage | αVβ3- MFGE8-PS (+) | Phagocytosis ↑, IL-6 ↓, TNF-α ↓ | Suppression | Miksa et al. (2006) |
| DC | miR-155, miR-146a | N/A | DC | miR-155: AGO-BACH1 (−), AGO-SHIP1 (−), miR-146a: IRAK1 (−), TRAF6 (−) | miR-155: IL-6 ↑, miR-146a: IL-10 ↑, IL-6↓, IL-12p40 ↓ | Activation/Suppression | Alexander et al. (2015) |
| DC (LMoDC) | EVs: HLA-1, ICAM-1, miR-155, CD63 | N/A | CD8+ T cell | MHC-peptide complex | CD8+ T cell activation ↑, TNF ↑, IFN ↑ | Activation | Lindenbergh et al. (2019) |
| Treg | EVs a : miR-142-3p, miR-150-5p | N/A | DC | ICAM-1/LFA-1 (+) | IL-6 ↓, IL-10 ↑, MHC-II ↓, CD80 ↓ | Suppression | Tung et al. (2018) |
| Treg | miR-155, let-7b, let-7d | Rab27, ceramide | Th1 cell | COX2 (+) | IFN-γ ↓, T cell proliferation ↓ | Suppression | Okoye et al. (2014) |
| B cell | miR-155 inhibitor | N/A | Macrophage | N/A | TNF-α↓, SOCS1 mRNA↑ | Suppression | Momen-Heravi et al. (2014) |
| B cell | MHC-peptide complex | Igα/β, TCR | CD4+ T cell | MHC-peptide-TCR (+) | CD4+ T cell activation ↑, antigen specific memory T cells ↑ | Activation | Muntasell et al. (2007) |
| CD8+T cell | TCR, FasL | TCR-MHC-I CD54-LFA-1 | DC (direct) CD8+T cell (indirect) | TCR-MHC-I (−) FasL-FasL (+) | DC antigen presentation ↓, apoptosis ↑, CD8+ CTL ↓ | Suppression | Xie et al. (2010) |
| T cell | MP a : Monocyte activating factors | N/A | Monocyte/macrophage | N/A | TNF-α ↑, IL-1 ↑, SIL-Ira ↑ | Activation | Scanu et al. (2008) |
| MDSC (inhibitory phenotype) | lncRNA (Hotairm1) | N/A | MDSC (activation phenotype) | S100A9 nuclear translocation +＋) | S100A9 release ↓, pro-inflammatory cytokines ↓, MDSCs transfer to inhibitory phenotype | Suppression | Alkhateeb et al. (2020) |
| G-MDSC | N/A | N/A | Neutrophil Monocyte/macrophage | L-arginine metabolism (−), ROS (−) | Neutrophil and monocyte/macrophage infiltration ↓, Th1 proliferation ↓, Treg ↑, IFN-γ ↓, TNF-α ↓ | Suppression | Wang et al. (2016) |
a
Exosomes are subsets of EVs or MVs, however, their immunomodulatory effects may exist unpredictable differences.