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Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury
Published on: May 21, 2018
Mesenchymal Stem Cell-Derived Exosomes Attenuate Murine Cytomegalovirus-Infected Pneumonia via NF-κB/NLRP3 Signaling
Fei Chen1,2, Zhida Chen1, Hui-Ting Wu1
1Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Sixth Affiliated Hospital, School of Basic Medical Science, Guangzhou Medical University, Guangzhou 511436, China.
Abstract:
Reactivation and infection with cytomegalovirus (CMV) are frequently observed in recipients of solid organ transplants, bone marrow transplants, and individuals with HIV infection. This presents an increasing risk of allograft rejection, opportunistic infection, graft failure, and patient mortality. Among immunocompromised hosts, interstitial pneumonia is the most critical clinical manifestation of CMV infection. Recent studies have demonstrated the potential therapeutic benefits of exosomes derived from mesenchymal stem cells (MSC-exos) in preclinical models of acute lung injury, including pneumonia, ARDS, and sepsis. However, the role of MSC-exos in the pathogenesis of infectious viral diseases, such as CMV pneumonia, remains unclear. In a mouse model of murine CMV-induced pneumonia, we observed that intravenous administration of mouse MSC (mMSC)-exos reduced lung damage, decreased the hyperinflammatory response, and shifted macrophage polarization from the M1 to the M2 phenotype. Treatment with mMSC-exos also significantly reduced the infiltration of inflammatory cells and pulmonary fibrosis. Furthermore, in vitro studies revealed that mMSC-exos reversed the hyperinflammatory phenotype of bone marrow-derived macrophages infected with murine CMV. Mechanistically, mMSC-exos treatment decreased activation of the NF-κB/NLRP3 signaling pathway both in vivo and in vitro. In summary, our findings indicate that mMSC-exo treatment is effective in severe CMV pneumonia by reducing lung inflammation and fibrosis through the NF-κB/NLRP3 signaling pathway, thus providing promising therapeutic potential for clinical CMV infection.
Insights
Mesenchymal stem cell-derived exosomes (MSC-exos) show promise in treating cytomegalovirus (CMV) pneumonia. This study found MSC-exos reduced lung inflammation and fibrosis in a mouse model by targeting the NF-κB/NLRP3 pathway.
Area of Science:
- Immunology
- Virology
- Regenerative Medicine
Background:
- Cytomegalovirus (CMV) infection poses significant risks, including pneumonia, in immunocompromised individuals like transplant recipients and those with HIV.
- Mesenchymal stem cell-derived exosomes (MSC-exos) have shown therapeutic potential in preclinical models of lung injury.
- The efficacy of MSC-exos in treating viral lung infections like CMV pneumonia is not well understood.
Purpose of the Study:
- To investigate the therapeutic potential of mouse mesenchymal stem cell-derived exosomes (mMSC-exos) in a murine model of cytomegalovirus (CMV) pneumonia.
- To elucidate the underlying mechanisms by which mMSC-exos exert their effects on CMV-induced lung inflammation and damage.
Main Methods:
- A mouse model of murine CMV-induced pneumonia was established.
- Intravenous administration of mMSC-exos was performed in infected mice.
- In vitro studies utilized bone marrow-derived macrophages infected with murine CMV.
- Analysis included assessment of lung damage, inflammatory response, macrophage polarization, cellular infiltration, fibrosis, and the NF-κB/NLRP3 signaling pathway.
Main Results:
- Treatment with mMSC-exos significantly reduced lung damage and the hyperinflammatory response in the mouse model.
- mMSC-exos therapy promoted a shift in macrophage polarization from M1 to M2 phenotype.
- In vitro, mMSC-exos reversed the hyperinflammatory phenotype of CMV-infected macrophages.
- mMSC-exos treatment suppressed the activation of the NF-κB/NLRP3 signaling pathway both in vivo and in vitro, reducing inflammation and pulmonary fibrosis.
Conclusions:
- mMSC-exos demonstrate significant therapeutic efficacy against severe CMV pneumonia in a preclinical setting.
- The mechanism involves the reduction of lung inflammation and fibrosis, potentially mediated by modulating the NF-κB/NLRP3 signaling pathway.
- MSC-exos represent a promising therapeutic strategy for managing clinical cytomegalovirus infections, particularly pneumonia.
