Table 2 Regulation of inflammatory pathways by viruses through exosomes

Respiratory syncytial viruses

RSV-infected A549 cells

–

In vitro (RSV-infected A549 cells)

Induction

Exosomes derived from RSV-infected A549 cells secrete significantly higher levels of RANTES, IP-10, and TNF-α, which activate the innate immune response and may through the release of pro-inflammatory cytokines and apoptosis in receptor cells have antiviral effects

[101]

Influenza

Respiratory epithelial cell lines

NP, NS1, M1, HA

In vitro (Respiratory epithelial cell lines)

Inhibition

Exosomes derived from respiratory epithelial cell lines infected with influenza virus showed an anti-viral response, which may inhibit inflammation in the early stages

[106]

Influenza

Bronchial alveolar lavage fluid (BALf) of influenza virus

–

In vitro (bronchial alveolar lavage fluid (BALf) of influenza virus)

Induction

Exosomes derived from bronchial alveolar lavage fluid (BALf) of influenza virus produce IL-6, MCP-1, and TNF, which are inflammatory cytokines and increase inflammation

[106]

Influenza

Macrophages, fibroblasts, T cell, and B cell lines

Nucleoprotein (NP) and non-structural protein (NS1)

In vitro (macrophages, fibroblasts, T cell, and B cell lines)

Induction

Levels of pro-inflammatory cytokines, such as IFN-γ, IL-1β, and CXCL8, were also elevated by the exosomes

[136]

Influenza

Bronchoalveolar lavage fluid (BALF)

miR-483-3p

In vitro (bronchoalveolar lavage fluid (BALF))

Induction

The transfer of miR-483-3p from bronchoalveolar lavage fluid (BALF) caused the expression of type I interferon and proinflammatory cytokine genes and strengthened their face

[137]

Influenza

Exosomes derived from H5N1-infected chickens

Viral proteins, NP and NS1

In vitro (exosomes derived from H5N1-infected chickens)

Induction

The presence of viral proteins such as NP and NS1 in exosomes derived from H5N1-infected chickens increases the level of pro-inflammatory cytokines such as IFN-γ, IL-1β, and IL-8

[119]

Influenza

Bronchoalveolar lavage fluid (BALF)

miR-483-3p, miR-374c-5p, miR-466i-5p, miR-203-3p

In vitro (bronchoalveolar lavage fluid (BALF))

Induction

miR-483-3p, miR-374c-5p, miR-466i-5p, miR-203-3p in exosomes derived from bronchoalveolar lavage fluid (BALF) significantly increased IFN-β expression, proinflammatory cytokine gene expression, and upregulates interferon-stimulated genes (ISGs), including IL6, CCL2, TNF-α, and SP110

[138]

Parainfluenza

Madin–Darby bovine kidney (MDBK) cells inoculated with CPIV3

miRNA 11

In vitro (Madin–Darby bovine kidney (MDBK) cells inoculated with CPIV3)

Unknown

These exosomes could transfer CPIV3 genetic materials to recipient cells to establish a productive infection and promote viral replication

[139]

Rhinoviruses

Primary bone marrow-derived DCs (BMDCs)

MiR155

in vitro and in vivo

Induction

miR-155 in exosomes derived from primary bone marrow-derived DCs (BMDCs) is essential for Th2-mediated eosinophilic inflammation in the lung and induces inflammatory conditions in the body

[118]

Rhinoviruses

RV-infected AECs

–

In vitro

Induction

Exosomes from RV-infected AECs yielded significant inflammatory cytokines/chemokines such as CXCL8, which induced an inflammatory state in the body

[140]

Rhinoviruses

Bronchoalveolar lavage fluid

–

In vitro

Induction

–

[141]

Coronaviruses

Lung macrophages

Nsp12 and Nsp13

In vitro

Induction

Nsp12 and Nsp13 in exosomes derived from lung macrophages lead to the activation of nuclear factor κB (NF-κB) and subsequent induction of an array of inflammatory cytokines

[127]

Coronaviruses

Patient plasma

Tenascin-C (TNC) and fibrinogen-β (FGB)

In vitro

Induction

Tenascin-C (TNC) and fibrinogen-β (FGB) induce the production of pro-inflammatory cytokines through interaction with the NF-κB inflammatory signaling pathway. FGB is transported via plasma exosomes and potentially induces pro-inflammatory cytokine signals in distant organ cells

[128]

Coronaviruses

A549 cell

Viral protein E, Nsp7, Nsp10, Nsp12, Nsp13, and slight protein M

In vitro

Induction

The RNA polymerase, Nsp12, alone inhibits tumor necrosis factor (TNF)-α and interleukin (IL)-6. Furthermore, a synergistic effect of Nsp12 working with Nsp13 was observed where, compared to Nsp12 alone, there was a significant induction of TNF-α, IL-1β, and IL-6, which are inflammatory cytokines. In contrast, M protein, Nsp13 alone, or Nsp10 did not

[127]

Coronaviruses

Endothelial cells

–

In vitro

Induction

Exosomes derived from endothelial cells infected with coronaviruses lead to NLRP3 inflammasome activation in endothelial cells of distant organs, which ultimately leads to IL-1β secretion and inflammatory response

[128]

Adenoviruses

Bone marrow-derived dendritic cells (DCs)

Expressing viral IL-10

In vitro

Inhibition

[142]

Adenoviruses

Derived from FasL-expressing DC

–

In vitro

Inhibition

Mice are immunized with a specific antigen, keyhole limpet hemocyanin (KLH). Then a Th1-mediated inflammatory response is induced 10 to 14 days after immunization by injection of the particular antigen into the hind pads. Mice immunized with KLH 106 DC or 1 μg exosome received in one hind paw 12 h before KLH booster injection into both hind paws. Delivery of DC/FasL or DC/FasL-derived exosomes significantly reduced paw swelling not only in the treated paw but also in the contralateral paw. Untreated suppressed 24, 48, and 72 h after antigen injection. These results show that genetically modified DC-expressing FasL as well as DC/FasL-derived exosomes are equally effective in suppressing the DTH response not only in the treated paw, but they are also in the untreated opposite paw

[135]

Adenovirus

Infected A549

–

In vitro

Induction

A549-derived exosomes infected with adenoviruses significantly increased IL-1β protein, which induced inflammatory conditions in the body

[134]